Variant X-48969669-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_004979.6(KCND1):c.603C>T(p.Ile201=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000233 in 1,209,381 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 94 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., 15 hem., cov: 24)

Exomes 𝑓: 0.00022 ( 0 hom. 79 hem. )

Consequence

KCND1
NM_004979.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.424

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant X-48969669-G-A is Benign according to our data. Variant chrX-48969669-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2660495.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.424 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 15 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCND1	NM_004979.6 linkuse as main transcript	c.603C>T	p.Ile201=	synonymous_variant	1/6	ENST00000218176.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCND1	ENST00000218176.4 linkuse as main transcript	c.603C>T	p.Ile201=	synonymous_variant	1/6	1	NM_004979.6	P1	Q9NSA2-1

Frequencies

GnomAD3 genomes

AF:

0.000407

AC:

AN:

112915

Hom.:

Cov.:

AF XY:

0.000428

AC XY:

AN XY:

35051

show subpopulations

Gnomad AFR

AF:

0.0000963

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00279

Gnomad ASJ

AF:

0.00113

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00844

Gnomad NFE

AF:

0.000131

Gnomad OTH

AF:

0.000659

GnomAD3 exomes

AF:

0.000340

AC:

AN:

176318

Hom.:

AF XY:

0.000286

AC XY:

AN XY:

62866

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00133

Gnomad ASJ exome

AF:

0.000819

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000142

Gnomad OTH exome

AF:

0.00160

GnomAD4 exome

AF:

0.000215

AC:

236

AN:

1096412

Hom.:

Cov.:

AF XY:

0.000218

AC XY:

AN XY:

362262

show subpopulations

Gnomad4 AFR exome

AF:

0.000152

Gnomad4 AMR exome

AF:

0.00162

Gnomad4 ASJ exome

AF:

0.00155

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000371

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000113

Gnomad4 OTH exome

AF:

0.000630

GnomAD4 genome

AF:

0.000407

AC:

AN:

112969

Hom.:

Cov.:

AF XY:

0.000427

AC XY:

AN XY:

35115

show subpopulations

Gnomad4 AFR

AF:

0.0000961

Gnomad4 AMR

AF:

0.00278

Gnomad4 ASJ

AF:

0.00113

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000131

Gnomad4 OTH

AF:

0.000651

Alfa

AF:

0.000608

Hom.:

Bravo

AF:

0.000627

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

Aug 01, 2022

KCND1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

2.0

DANN

Benign

0.91

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