1-111982352-C-T

Position:

chr1-111982352-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001378969.1(KCND3):c.375G>A(p.Pro125=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00964 in 1,614,078 control chromosomes in the GnomAD database, including 581 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 97 hom., cov: 32)

Exomes 𝑓: 0.0082 ( 484 hom. )

Consequence

KCND3
NM_001378969.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -1.67

Variant links:

Genes affected

KCND3 (HGNC:6239): (potassium voltage-gated channel subfamily D member 3) Voltage-gated potassium (Kv) 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. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shal-related subfamily, members of which form voltage-activated A-type potassium ion channels and are prominent in the repolarization phase of the action potential. This member includes two isoforms with different sizes, which are encoded by alternatively spliced transcript variants of this gene. [provided by RefSeq, Jul 2008]

KCND3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 1-111982352-C-T is Benign according to our data. Variant chr1-111982352-C-T is described in ClinVar as [Benign]. Clinvar id is 380951.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-111982352-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.67 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCND3	NM_001378969.1 linkuse as main transcript	c.375G>A	p.Pro125=	synonymous_variant	2/8	ENST00000302127.5	NP_001365898.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCND3	ENST00000302127.5 linkuse as main transcript	c.375G>A	p.Pro125=	synonymous_variant	2/8	5	NM_001378969.1	ENSP00000306923	P3	Q9UK17-1

Frequencies

GnomAD3 genomes

AF:

0.0231

AC:

3511

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0607

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0157

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.0960

Gnomad SAS

AF:

0.0210

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00118

Gnomad OTH

AF:

0.0234

GnomAD3 exomes

AF:

0.0186

AC:

4681

AN:

251386

Hom.:

151

AF XY:

0.0163

AC XY:

2220

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.0616

Gnomad AMR exome

AF:

0.0277

Gnomad ASJ exome

AF:

0.000595

Gnomad EAS exome

AF:

0.100

Gnomad SAS exome

AF:

0.0206

Gnomad FIN exome

AF:

0.00277

Gnomad NFE exome

AF:

0.000985

Gnomad OTH exome

AF:

0.0111

GnomAD4 exome

AF:

0.00824

AC:

12044

AN:

1461880

Hom.:

484

Cov.:

AF XY:

0.00831

AC XY:

6045

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0645

Gnomad4 AMR exome

AF:

0.0251

Gnomad4 ASJ exome

AF:

0.000574

Gnomad4 EAS exome

AF:

0.129

Gnomad4 SAS exome

AF:

0.0193

Gnomad4 FIN exome

AF:

0.00285

Gnomad4 NFE exome

AF:

0.000847

Gnomad4 OTH exome

AF:

0.0132

GnomAD4 genome

AF:

0.0231

AC:

3521

AN:

152198

Hom.:

Cov.:

AF XY:

0.0232

AC XY:

1726

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0607

Gnomad4 AMR

AF:

0.0160

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.0961

Gnomad4 SAS

AF:

0.0206

Gnomad4 FIN

AF:

0.00217

Gnomad4 NFE

AF:

0.00118

Gnomad4 OTH

AF:

0.0232

Alfa

AF:

0.00595

Hom.:

Bravo

AF:

0.0266

Asia WGS

AF:

0.0570

AC:

199

AN:

3478

EpiCase

AF:

0.00174

EpiControl

AF:

0.00148

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 26, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 09, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Oct 15, 2019	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 09, 2015

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. -

Spinocerebellar ataxia type 19/22

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

1.1

DANN

Benign

0.89

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over