rs759773311

Variant names:

• chr11-17736435-G-A
• NM_001112741.2:c.433G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-17736435-G-A
• chr11-17736435-G-C
• chr11-17736435-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001112741.2(KCNC1):​c.433G>A​(p.Gly145Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,453,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: KCNC1 NM_001112741.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.48

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17673045).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNC1	NM_001112741.2	c.433G>A	p.Gly145Ser	missense_variant	Exon 1 of 4	ENST00000265969.8	NP_001106212.1
KCNC1	NM_004976.4	c.433G>A	p.Gly145Ser	missense_variant	Exon 1 of 2		NP_004967.1
KCNC1	XM_047426916.1	c.433G>A	p.Gly145Ser	missense_variant	Exon 1 of 4		XP_047282872.1
KCNC1	XR_930866.3	n.1655G>A		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNC1	ENST00000265969.8	c.433G>A	p.Gly145Ser	missense_variant	Exon 1 of 4	5	NM_001112741.2	ENSP00000265969.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1453952 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 723272

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 9.01e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	32
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T;.
Eigen	Benign	-0.023
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.075	D
MetaRNN	Benign	0.18	T;T
MetaSVM	Uncertain	0.34	D
MutationAssessor	Benign	1.1	L;L
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.15	N;N
REVEL	Uncertain	0.40
Sift	Benign	0.71	T;T
Sift4G	Benign	0.72	T;T
Polyphen		0.61	P;.
Vest4		0.27
MutPred		0.27		Gain of phosphorylation at G145 (P = 0.0052);Gain of phosphorylation at G145 (P = 0.0052);
MVP		0.80
MPC		1.6
ClinPred		0.91	D
GERP RS		5.2
Varity_R		0.15
gMVP		0.70

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-17757982; COSMIC: COSV56391843;