Variant 8-109972531-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014379.4(KCNV1):c.718C>A(p.Gln240Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

KCNV1
NM_014379.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.39

Variant links:

Genes affected

KCNV1 (HGNC:18861): (potassium voltage-gated channel modifier subfamily V member 1) Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a member of the potassium voltage-gated channel subfamily V. This protein is essentially present in the brain, and its role might be to inhibit the function of a particular class of outward rectifier potassium channel types. [provided by RefSeq, Jul 2008]

KCNV1 links:

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ACMG classification

Classification made for transcript

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=0.270571).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNV1	NM_014379.4 linkuse as main transcript	c.718C>A	p.Gln240Lys	missense_variant	3/4	ENST00000524391.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNV1	ENST00000524391.6 linkuse as main transcript	c.718C>A	p.Gln240Lys	missense_variant	3/4	1	NM_014379.4	P1
KCNV1	ENST00000297404.1 linkuse as main transcript	c.718C>A	p.Gln240Lys	missense_variant	2/3	1		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251476

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.00000137

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 27, 2023

The c.718C>A (p.Q240K) alteration is located in exon 2 (coding exon 2) of the KCNV1 gene. This alteration results from a C to A substitution at nucleotide position 718, causing the glutamine (Q) at amino acid position 240 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Uncertain

0.031

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Uncertain

0.56

D;D

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.036

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.74

.;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.27

T;T

MetaSVM

Uncertain

0.50

MutationAssessor

Benign

1.1

L;L

MutationTaster

Benign

0.62

N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.75

N;N

REVEL

Benign

0.29

Sift

Benign

0.23

T;T

Sift4G

Benign

0.56

T;T

Polyphen

0.0080

B;B

Vest4

0.21

MutPred

0.52

Gain of ubiquitination at Q240 (P = 0.0428);Gain of ubiquitination at Q240 (P = 0.0428);

MVP

0.80

MPC

1.4

ClinPred

0.10

GERP RS

4.7

Varity_R

0.28

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over