rs139034501

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_020822.3(KCNT1):c.30G>A(p.Pro10Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00786 in 1,608,588 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P10P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0052 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0081 ( 82 hom. )

Consequence

KCNT1
NM_020822.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -1.43

Publications

4 publications found

Variant links:

Genes affected

KCNT1 (HGNC:18865): (potassium sodium-activated channel subfamily T member 1) Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a sodium-activated potassium channel subunit which is thought to function in ion conductance and developmental signaling pathways. Mutations in this gene cause the early-onset epileptic disorders, malignant migrating partial seizures of infancy and autosomal dominant nocturnal frontal lobe epilepsy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

KCNT1 links:

SOHLH1 (HGNC:27845): (spermatogenesis and oogenesis specific basic helix-loop-helix 1) This gene encodes one of testis-specific transcription factors which are essential for spermatogenesis, oogenesis and folliculogenesis. This gene is located on chromosome 9. Mutations in this gene are associated with nonobstructive azoospermia. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2013]

SOHLH1 Gene-Disease associations (from GenCC):

ovarian dysgenesis 5
Inheritance: AR, AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
hypogonadism
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

SOHLH1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 9-135702288-G-A is Benign according to our data. Variant chr9-135702288-G-A is described in ClinVar as [Benign]. Clinvar id is 193440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.43 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00522 (795/152156) while in subpopulation SAS AF = 0.0162 (78/4824). AF 95% confidence interval is 0.0133. There are 5 homozygotes in GnomAd4. There are 395 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 795 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNT1	NM_020822.3 link	c.30G>A	p.Pro10Pro	synonymous_variant	Exon 1 of 31	ENST00000371757.7	NP_065873.2	Q5JUK3-3
KCNT1	NM_001272003.2 link	c.30G>A	p.Pro10Pro	synonymous_variant	Exon 1 of 31		NP_001258932.1	Q5JUK3-4
SOHLH1	XM_011518698.4 link	c.-2184C>T		upstream_gene_variant			XP_011517000.1
SOHLH1	XM_006717109.5 link	c.-2313C>T		upstream_gene_variant			XP_006717172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNT1	ENST00000371757.7 link	c.30G>A	p.Pro10Pro	synonymous_variant	Exon 1 of 31	1	NM_020822.3	ENSP00000360822.2		Q5JUK3-3

Frequencies

GnomAD3 genomes

AF:

0.00524

AC:

797

AN:

152038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.00989

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.0150

Gnomad EAS

AF:

0.00406

Gnomad SAS

AF:

0.0162

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.0350

Gnomad NFE

AF:

0.00719

Gnomad OTH

AF:

0.00527

GnomAD2 exomes

AF:

0.00672

AC:

1581

AN:

235382

AF XY:

0.00764

show subpopulations

Gnomad AFR exome

AF:

0.00125

Gnomad AMR exome

AF:

0.00370

Gnomad ASJ exome

AF:

0.0157

Gnomad EAS exome

AF:

0.000925

Gnomad FIN exome

AF:

0.000424

Gnomad NFE exome

AF:

0.00740

Gnomad OTH exome

AF:

0.00749

GnomAD4 exome

AF:

0.00813

AC:

11846

AN:

1456432

Hom.:

Cov.:

AF XY:

0.00842

AC XY:

6102

AN XY:

724562

show subpopulations

African (AFR)

AF:

0.00169

AC:

AN:

33108

American (AMR)

AF:

0.00357

AC:

159

AN:

44498

Ashkenazi Jewish (ASJ)

AF:

0.0155

AC:

402

AN:

25934

East Asian (EAS)

AF:

0.0145

AC:

572

AN:

39370

South Asian (SAS)

AF:

0.0146

AC:

1254

AN:

86074

European-Finnish (FIN)

AF:

0.000347

AC:

AN:

51802

Middle Eastern (MID)

AF:

0.0298

AC:

170

AN:

5714

European-Non Finnish (NFE)

AF:

0.00788

AC:

8741

AN:

1109792

Other (OTH)

AF:

0.00788

AC:

474

AN:

60140

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

576

1152

1729

2305

2881

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00522

AC:

795

AN:

152156

Hom.:

Cov.:

AF XY:

0.00531

AC XY:

395

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.00123

AC:

AN:

41530

American (AMR)

AF:

0.00464

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0150

AC:

AN:

3466

East Asian (EAS)

AF:

0.00407

AC:

AN:

5156

South Asian (SAS)

AF:

0.0162

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00718

AC:

488

AN:

67958

Other (OTH)

AF:

0.00521

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

125

166

208

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00401

Hom.:

Bravo

AF:

0.00519

Asia WGS

AF:

0.00577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 08, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 02, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 22, 2024

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

KCNT1: BP4, BP7, BS1, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Developmental and epileptic encephalopathy, 14;C3554306:Autosomal dominant nocturnal frontal lobe epilepsy 5

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

May 17, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Developmental and epileptic encephalopathy, 14

Benign:1

Mar 15, 2022

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal dominant nocturnal frontal lobe epilepsy 5

Benign:1

Mar 15, 2022

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

2.3

(source)

DANN

Benign

0.80

PhyloP100

-1.4

PromoterAI

-0.0084

Neutral

(source)

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs139034501

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over