11-17779535-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_001112741.2(KCNC1):c.1584C>T(p.Pro528=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 1,551,206 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. P528P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00022 (1 hom., cov: 33)
  • Exomes 𝑓: 0.000096 (1 hom.)
• Consequence: KCNC1 NM_001112741.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00400

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 11-17779535-C-T is Benign according to our data. Variant chr11-17779535-C-T is described in ClinVar as [Benign]. Clinvar id is 1166035.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.004 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000217 (33/152170) while in subpopulation SAS AF= 0.000829 (4/4828). AF 95% confidence interval is 0.000283. There are 1 homozygotes in gnomad4. There are 28 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 33 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNC1	NM_001112741.2	c.1584C>T	p.Pro528=	synonymous_variant	3/4	ENST00000265969.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNC1	ENST00000265969.8	c.1584C>T	p.Pro528=	synonymous_variant	3/4	5	NM_001112741.2	P1

Frequencies

GnomAD3 genomes AF: 0.000217 AC: 33 AN: 152170 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00273

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000267 AC: 41 AN: 153810 Hom.: 0 AF XY: 0.000282 AC XY: 23 AN XY: 81600

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000132

Gnomad FIN exome AF: 0.00236

Gnomad NFE exome AF: 0.0000336

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000958 AC: 134 AN: 1399036 Hom.: 1 Cov.: 31 AF XY: 0.000104 AC XY: 72 AN XY: 690044

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000280

Gnomad4 SAS exome AF: 0.000101

Gnomad4 FIN exome AF: 0.00201

Gnomad4 NFE exome AF: 0.0000204

Gnomad4 OTH exome AF: 0.0000690

GnomAD4 genome AF: 0.000217 AC: 33 AN: 152170 Hom.: 1 Cov.: 33 AF XY: 0.000377 AC XY: 28 AN XY: 74330

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00273

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Progressive myoclonic epilepsy type 7 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 22, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
Cadd	Benign	11
Dann	Benign	0.85

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: rs1044982783; hg19: chr11-17801082;