Genetic Variant KCNV1:p.Ser162Arg (chr8-109972765-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014379.4(KCNV1):c.484A>C(p.Ser162Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,456,734 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. S162G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

KCNV1
NM_014379.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.44

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22093731).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNV1	NM_014379.4 link	c.484A>C	p.Ser162Arg	missense_variant	Exon 3 of 4	ENST00000524391.6	NP_055194.1	Q6PIU1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNV1	ENST00000524391.6 link	c.484A>C	p.Ser162Arg	missense_variant	Exon 3 of 4	1	NM_014379.4	ENSP00000435954.1		Q6PIU1
KCNV1	ENST00000297404.1 link	c.484A>C	p.Ser162Arg	missense_variant	Exon 2 of 3	1		ENSP00000297404.1		Q6PIU1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1456734

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724384

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33100

American (AMR)

AF:

0.00

AC:

AN:

43908

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25878

East Asian (EAS)

AF:

0.00

AC:

AN:

39668

South Asian (SAS)

AF:

0.00

AC:

AN:

85282

European-Finnish (FIN)

AF:

0.0000189

AC:

AN:

52860

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110166

Other (OTH)

AF:

0.00

AC:

AN:

60146

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.20

T;T

Eigen

Benign

-0.043

Eigen_PC

Benign

0.13

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.82

.;T

M_CAP

Uncertain

0.096

MetaRNN

Benign

0.22

T;T

MetaSVM

Uncertain

0.50

MutationAssessor

Benign

1.3

L;L

PhyloP100

5.4

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.51

N;N

REVEL

Uncertain

0.47

Sift

Benign

0.33

T;T

Sift4G

Benign

0.55

T;T

Polyphen

0.32

B;B

Vest4

0.30

MutPred

0.22

Loss of phosphorylation at S162 (P = 0.02);Loss of phosphorylation at S162 (P = 0.02);

MVP

0.66

MPC

1.3

ClinPred

0.62

GERP RS

5.0

Varity_R

0.22

gMVP

0.60

Mutation Taster

=44/56

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over