X-48962803-A-G

Position:

• chrX-48962803-A-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_004979.6(KCND1):​c.1722T>C​(p.Arg574Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.92 (33135 hom., 29833 hem., cov: 22)
  • Exomes 𝑓: 0.99 (361223 hom. 360029 hem.)
  • Failed GnomAD Quality Control
• Consequence: KCND1 NM_004979.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.199

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]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant X-48962803-A-G is Benign according to our data. Variant chrX-48962803-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 769212.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.199 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCND1	NM_004979.6	c.1722T>C	p.Arg574Arg	synonymous_variant	6/6	ENST00000218176.4	NP_004970.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCND1	ENST00000218176.4	c.1722T>C	p.Arg574Arg	synonymous_variant	6/6	1	NM_004979.6	ENSP00000218176.3
KCND1	ENST00000376477.5	c.591T>C	p.Arg197Arg	synonymous_variant	5/5	2		ENSP00000365660.1

Frequencies

GnomAD3 genomes AF: 0.916 AC: 100858 AN: 110087 Hom.: 33144 Cov.: 22 AF XY: 0.922 AC XY: 29785 AN XY: 32293

Gnomad AFR AF: 0.709

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.967

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.996

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.939

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.992 AC: 1087632 AN: 1096952 Hom.: 361223 Cov.: 36 AF XY: 0.994 AC XY: 360029 AN XY: 362384

Gnomad4 AFR exome AF: 0.709

Gnomad4 AMR exome AF: 0.985

Gnomad4 ASJ exome AF: 0.999

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.982

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.916 AC: 100890 AN: 110141 Hom.: 33135 Cov.: 22 AF XY: 0.922 AC XY: 29833 AN XY: 32357

Gnomad4 AFR AF: 0.709

Gnomad4 AMR AF: 0.967

Gnomad4 ASJ AF: 0.999

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.940

Alfa AF: 0.982 Hom.: 47588

Bravo AF: 0.904

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	2.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3027483; hg19: chrX-48820064;