11-17779576-G-C

Position:

• chr11-17779576-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001112741.2(KCNC1):​c.1625G>C​(p.Arg542Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000143 in 1,399,248 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: KCNC1 NM_001112741.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.57

Genes affected

KCNC1 (HGNC:6233): (potassium voltage-gated channel subfamily C member 1) This gene encodes a member of a family of integral membrane proteins that mediate the voltage-dependent potassium ion permeability of excitable membranes. Alternative splicing is thought to result in two transcript variants encoding isoforms that differ at their C-termini. These isoforms have had conflicting names in the literature: the longer isoform has been called both "b" and "alpha", while the shorter isoform has been called both "a" and "beta" (PMIDs 1432046, 12091563). [provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNC1	NM_001112741.2	c.1625G>C	p.Arg542Thr	missense_variant	3/4	ENST00000265969.8	NP_001106212.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNC1	ENST00000265969.8	c.1625G>C	p.Arg542Thr	missense_variant	3/4	5	NM_001112741.2	ENSP00000265969.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000130 AC: 2 AN: 153826 Hom.: 0 AF XY: 0.0000245 AC XY: 2 AN XY: 81636

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000812

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1399248 Hom.: 0 Cov.: 31 AF XY: 0.00000290 AC XY: 2 AN XY: 690164

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000561

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	26
DANN	Benign	0.97
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Pathogenic	0.99	D
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-2.3	N
REVEL	Pathogenic	0.72
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.011	D
Vest4		0.41
MutPred		0.37		Gain of phosphorylation at R542 (P = 0.0079);
MVP		0.93
MPC		2.6
ClinPred		0.65	D
GERP RS		5.7
gMVP		0.68

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

Other links and lift over

dbSNP: rs1021551048; hg19: chr11-17801123;