Variant 8-36787341-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001031836.3(KCNU1):c.231T>A(p.His77Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,612,392 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: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

KCNU1
NM_001031836.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.441

Variant links:

Genes affected

KCNU1 (HGNC:18867): (potassium calcium-activated channel subfamily U member 1) This gene encodes a member of the potassium channel family of proteins. The encoded voltage-gated ion channel allows the outward flow of potassium ions during plasma membrane hyperpolarization in sperm. Opening of this channel may be regulated by calcium ion levels. Homozygous knockout mice that lack the related mouse gene exhibit male sterility. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

KCNU1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.034734905).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNU1	NM_001031836.3 linkuse as main transcript	c.231T>A	p.His77Gln	missense_variant	2/27	ENST00000399881.8	NP_001027006.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
KCNU1	ENST00000399881.8 linkuse as main transcript	c.231T>A	p.His77Gln	missense_variant	2/27	2	NM_001031836.3	ENSP00000382770	P1
KCNU1	ENST00000522372.5 linkuse as main transcript	c.231T>A	p.His77Gln	missense_variant, NMD_transcript_variant	2/28	1		ENSP00000428552
KCNU1	ENST00000523973.5 linkuse as main transcript	c.231T>A	p.His77Gln	missense_variant	2/8	5		ENSP00000429951
KCNU1	ENST00000522417.1 linkuse as main transcript	c.231T>A	p.His77Gln	missense_variant, NMD_transcript_variant	2/5	4		ENSP00000429149

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000242

AC:

AN:

247826

Hom.:

AF XY:

0.0000298

AC XY:

AN XY:

134410

show subpopulations

Gnomad AFR exome

AF:

0.000391

Gnomad AMR exome

AF:

0.00

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:

0.00000890

AC:

AN:

1460124

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726260

show subpopulations

Gnomad4 AFR exome

AF:

0.000359

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000144

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000174

ESP6500AA

AF:

0.000520

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000497

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

Jun 02, 2023

The c.231T>A (p.H77Q) alteration is located in exon 2 (coding exon 2) of the KCNU1 gene. This alteration results from a T to A substitution at nucleotide position 231, causing the histidine (H) at amino acid position 77 to be replaced by a glutamine (Q). 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

0.091

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.12

DANN

Benign

0.56

DEOGEN2

Benign

0.025

.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.24

T;T

M_CAP

Benign

0.0034

MetaRNN

Benign

0.035

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.84

.;L

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

0.14

N;N

REVEL

Benign

0.0090

Sift

Benign

0.41

T;T

Sift4G

Benign

0.42

T;T

Polyphen

0.0010

.;B

Vest4

0.047

MutPred

0.37

Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);

MVP

0.095

MPC

0.022

ClinPred

0.020

GERP RS

-5.3

Varity_R

0.033

gMVP

0.043

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

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