NM_004979.6:c.1591T>G

Variant names:

• chrX-48966182-A-C
• rs35743038
• NM_004979.6:c.1591T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004979.6(KCND1):​c.1591T>G​(p.Ser531Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00318 in 1,209,390 control chromosomes in the GnomAD database, including 76 homozygotes. There are 1,059 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (34 hom., 524 hem., cov: 23)
  • Exomes 𝑓: 0.0018 (42 hom. 535 hem.)
• Consequence: KCND1 NM_004979.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.86
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0047756433).
• BP6: Variant X-48966182-A-C is Benign according to our data. Variant chrX-48966182-A-C is described in ClinVar as Benign. ClinVar VariationId is 781549.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0539 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004979.6. 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
	KCND1	NM_004979.6	MANE Select	c.1591T>G	p.Ser531Ala	missense	Exon 5 of 6	NP_004970.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCND1	ENST00000218176.4	TSL:1 MANE Select	c.1591T>G	p.Ser531Ala	missense	Exon 5 of 6	ENSP00000218176.3	Q9NSA2-1
	KCND1	ENST00000935975.1		c.1603T>G	p.Ser535Ala	missense	Exon 5 of 6	ENSP00000606034.1
	KCND1	ENST00000935976.1		c.1588T>G	p.Ser530Ala	missense	Exon 5 of 6	ENSP00000606035.1

Frequencies

GnomAD3 genomes AF: 0.0164 AC: 1860 AN: 113149 Hom.: 34 Cov.: 23

Gnomad AFR AF: 0.0561

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00702

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000354

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00417

Gnomad NFE AF: 0.000225

Gnomad OTH AF: 0.0157

GnomAD2 exomes AF: 0.00467 AC: 831 AN: 177870 AF XY: 0.00304

Gnomad AFR exome AF: 0.0580

Gnomad AMR exome AF: 0.00240

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000130

Gnomad NFE exome AF: 0.000139

Gnomad OTH exome AF: 0.00300

GnomAD4 exome AF: 0.00181 AC: 1981 AN: 1096188 Hom.: 42 Cov.: 31 AF XY: 0.00148 AC XY: 535 AN XY: 362248

African (AFR) AF: 0.0608 AC: 1602 AN: 26369

American (AMR) AF: 0.00322 AC: 113 AN: 35085

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19228

East Asian (EAS) AF: 0.00 AC: 0 AN: 30182

South Asian (SAS) AF: 0.000149 AC: 8 AN: 53778

European-Finnish (FIN) AF: 0.0000496 AC: 2 AN: 40294

Middle Eastern (MID) AF: 0.00202 AC: 7 AN: 3470

European-Non Finnish (NFE) AF: 0.0000416 AC: 35 AN: 841818

Other (OTH) AF: 0.00466 AC: 214 AN: 45964

GnomAD4 genome AF: 0.0165 AC: 1863 AN: 113202 Hom.: 34 Cov.: 23 AF XY: 0.0148 AC XY: 524 AN XY: 35354

African (AFR) AF: 0.0561 AC: 1749 AN: 31194

American (AMR) AF: 0.00702 AC: 76 AN: 10832

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2659

East Asian (EAS) AF: 0.00 AC: 0 AN: 3580

South Asian (SAS) AF: 0.000355 AC: 1 AN: 2820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6325

Middle Eastern (MID) AF: 0.00457 AC: 1 AN: 219

European-Non Finnish (NFE) AF: 0.000225 AC: 12 AN: 53337

Other (OTH) AF: 0.0155 AC: 24 AN: 1550

Alfa AF: 0.00545 Hom.: 262

Bravo AF: 0.0186

ESP6500AA AF: 0.0511 AC: 196

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00534 AC: 648

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.46	T
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.0048	T
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	1.6	L
PhyloP100		5.9
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.30
Sift	Benign	0.033	D
Sift4G	Benign	0.15	T
Polyphen		0.080	B
Vest4		0.33
MVP		0.74
MPC		0.052
ClinPred		0.016	T
GERP RS		5.4
Varity_R		0.23
gMVP		0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs35743038; hg19: chrX-48822589;