rs371344625

Variant names:

• chr11-17771688-C-A
• NM_001112741.2:c.594C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-17771688-C-A
• chr11-17771688-C-G
• chr11-17771688-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001112741.2(KCNC1):​c.594C>A​(p.Phe198Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,712 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in Lovd.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: KCNC1 NM_001112741.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.07

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37923488).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNC1	NM_001112741.2	c.594C>A	p.Phe198Leu	missense_variant	Exon 2 of 4	ENST00000265969.8	NP_001106212.1
KCNC1	NM_004976.4	c.594C>A	p.Phe198Leu	missense_variant	Exon 2 of 2		NP_004967.1
KCNC1	XM_047426916.1	c.594C>A	p.Phe198Leu	missense_variant	Exon 2 of 4		XP_047282872.1
KCNC1	XR_930866.3	n.1816C>A		non_coding_transcript_exon_variant	Exon 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNC1	ENST00000265969.8	c.594C>A	p.Phe198Leu	missense_variant	Exon 2 of 4	5	NM_001112741.2	ENSP00000265969.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457712 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724120

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: 9.02e-7

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
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.81	D;.
Eigen	Benign	-0.10
Eigen_PC	Benign	0.087
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.38	T;T
MetaSVM	Uncertain	0.54	D
MutationAssessor	Benign	1.8	L;L
PrimateAI	Pathogenic	0.91	D
PROVEAN	Pathogenic	-4.6	D;D
REVEL	Uncertain	0.51
Sift	Benign	0.39	T;T
Sift4G	Benign	0.33	T;T
Polyphen		0.019	B;.
Vest4		0.48
MutPred		0.53		Loss of catalytic residue at F198 (P = 0.1674);Loss of catalytic residue at F198 (P = 0.1674);
MVP		0.69
MPC		1.8
ClinPred		0.98	D
GERP RS		4.8
Varity_R		0.64
gMVP		0.88

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: chr11-17793235;