Variant chrX-48966291-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_004979.6(KCND1):c.1482A>G(p.Thr494=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000936 in 1,068,878 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0000094 ( 0 hom. 0 hem. )

Consequence

KCND1
NM_004979.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.266

Variant links:

Genes affected

KCND1 (HGNC:6237): (potassium voltage-gated channel subfamily D member 1) This gene encodes a multipass membrane protein that comprises the pore subunit of the voltage-gated A-type potassium channel, which functions in the repolarization of membrane action potentials. Activity of voltage-gated potassium channels is important in a number of physiological processes, among them the regulation of neurotransmitter release, heart rate, insulin secretion, and smooth muscle contraction. [provided by RefSeq, Aug 2013]

KCND1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant X-48966291-T-C is Benign according to our data. Variant chrX-48966291-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2660492.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.266 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCND1	NM_004979.6 linkuse as main transcript	c.1482A>G	p.Thr494=	synonymous_variant	5/6	ENST00000218176.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCND1	ENST00000218176.4 linkuse as main transcript	c.1482A>G	p.Thr494=	synonymous_variant	5/6	1	NM_004979.6	P1	Q9NSA2-1
KCND1	ENST00000376477.5 linkuse as main transcript	c.351A>G	p.Thr117=	synonymous_variant	4/5	2			Q9NSA2-2
KCND1	ENST00000419374.1 linkuse as main transcript	c.198A>G	p.Thr66=	synonymous_variant	2/2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000304

AC:

AN:

131596

Hom.:

AF XY:

0.00

AC XY:

AN XY:

42546

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000554

Gnomad OTH exome

AF:

0.000278

GnomAD4 exome

AF:

0.00000936

AC:

AN:

1068878

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

347804

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000109

Gnomad4 OTH exome

AF:

0.0000222

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

KCND1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

1.3

DANN

Benign

0.49

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