NM_020822.3:c.15C>T

Variant names:

• chr9-135702273-C-T
• rs771669111
• NM_020822.3:c.15C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_020822.3(KCNT1):​c.15C>T​(p.Asp5Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000497 in 1,608,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: KCNT1 NM_020822.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0610
• Publications: 0 publications found

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]

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):

• spermatogenic failure 32

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
• ovarian dysgenesis 5

  Inheritance: AR, AD Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hypogonadism

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 9-135702273-C-T is Benign according to our data. Variant chr9-135702273-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1534507.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.061 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020822.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNT1	NM_020822.3	MANE Select	c.15C>T	p.Asp5Asp	synonymous	Exon 1 of 31	NP_065873.2	Q5JUK3-3
	KCNT1	NM_001272003.2		c.15C>T	p.Asp5Asp	synonymous	Exon 1 of 31	NP_001258932.1	Q5JUK3-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNT1	ENST00000371757.7	TSL:1 MANE Select	c.15C>T	p.Asp5Asp	synonymous	Exon 1 of 31	ENSP00000360822.2	Q5JUK3-3
	KCNT1	ENST00000460750.5	TSL:1	n.15C>T		non_coding_transcript_exon	Exon 1 of 32	ENSP00000418777.1	F8WC49
	KCNT1	ENST00000487664.5	TSL:5	c.15C>T	p.Asp5Asp	synonymous	Exon 1 of 32	ENSP00000417851.2	Q5JUK3-2

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152072 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000848 AC: 2 AN: 235904 AF XY: 0.0000153

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000293

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1456582 Hom.: 0 Cov.: 31 AF XY: 0.00000552 AC XY: 4 AN XY: 724568

African (AFR) AF: 0.00 AC: 0 AN: 33158

American (AMR) AF: 0.0000225 AC: 1 AN: 44510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25970

East Asian (EAS) AF: 0.00 AC: 0 AN: 39404

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51854

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1109724

Other (OTH) AF: 0.00 AC: 0 AN: 60154

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152072 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74284

African (AFR) AF: 0.0000483 AC: 2 AN: 41414

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67988

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Developmental and epileptic encephalopathy, 14;C3554306:Autosomal dominant nocturnal frontal lobe epilepsy 5 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	4.1
DANN	Benign	0.90
PhyloP100		-0.061
PromoterAI		-0.0080	Neutral

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

Other links and lift over

dbSNP: rs771669111; hg19: chr9-138594119;