Variant chrX-48966313-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP5BP4BS2_Supporting

The NM_004979.6(KCND1):c.1468-8G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000261 in 1,174,893 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 99 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely pathogenic (no stars).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., 10 hem., cov: 24)

Exomes 𝑓: 0.00027 ( 0 hom. 89 hem. )

Consequence

KCND1
NM_004979.6 splice_region, intron

Scores

Splicing: ADA: 0.0001119

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: -0.343

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 -1 ACMG points.

PP5

Variant X-48966313-C-A is Pathogenic according to our data. Variant chrX-48966313-C-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 599560.Status of the report is no_assertion_criteria_provided, 0 stars.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76). . Strength limited to SUPPORTING due to the PP5.

BS2

High Hemizygotes in GnomAd4 at 10 geneVariant has number of hemizygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCND1	NM_004979.6 linkuse as main transcript	c.1468-8G>T		splice_region_variant, intron_variant		ENST00000218176.4	NP_004970.3	Q9NSA2-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
KCND1	ENST00000218176.4 linkuse as main transcript	c.1468-8G>T	splice_region_variant, intron_variant	1	NM_004979.6	ENSP00000218176.3	Q9NSA2-1
KCND1	ENST00000376477.5 linkuse as main transcript	c.337-8G>T	splice_region_variant, intron_variant	2		ENSP00000365660.1	Q9NSA2-2
KCND1	ENST00000419374.1 linkuse as main transcript	c.181-8G>T	splice_region_variant, intron_variant	3		ENSP00000413989.1	H7C3V4

Frequencies

GnomAD3 genomes

AF:

0.000203

AC:

AN:

113451

Hom.:

Cov.:

AF XY:

0.000281

AC XY:

AN XY:

35585

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000790

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000337

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000202

AC:

AN:

123486

Hom.:

AF XY:

0.000123

AC XY:

AN XY:

40514

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:

0.000499

Gnomad NFE exome

AF:

0.000367

Gnomad OTH exome

AF:

0.000290

GnomAD4 exome

AF:

0.000268

AC:

284

AN:

1061442

Hom.:

Cov.:

AF XY:

0.000258

AC XY:

AN XY:

344796

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000357

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000707

Gnomad4 NFE exome

AF:

0.000307

Gnomad4 OTH exome

AF:

0.0000671

GnomAD4 genome

AF:

0.000203

AC:

AN:

113451

Hom.:

Cov.:

AF XY:

0.000281

AC XY:

AN XY:

35585

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000790

Gnomad4 NFE

AF:

0.000337

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000356

Hom.:

Bravo

AF:

0.000140

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Short stature

Pathogenic:1

Likely pathogenic, no assertion criteria provided

case-control

Institute of Human Genetics, FAU Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg

Nov 18, 2001

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

4.7

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.0

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