Variant chr8-36804055-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001031836.3(KCNU1):c.344G>T(p.Gly115Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000213 in 1,407,706 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

KCNU1
NM_001031836.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.15

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNU1	NM_001031836.3 linkuse as main transcript	c.344G>T	p.Gly115Val	missense_variant	3/27	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.344G>T	p.Gly115Val	missense_variant	3/27	2	NM_001031836.3	ENSP00000382770	P1
KCNU1	ENST00000522372.5 linkuse as main transcript	c.344G>T	p.Gly115Val	missense_variant, NMD_transcript_variant	3/28	1		ENSP00000428552
KCNU1	ENST00000523973.5 linkuse as main transcript	c.344G>T	p.Gly115Val	missense_variant	3/8	5		ENSP00000429951
KCNU1	ENST00000522417.1 linkuse as main transcript	c.316-1140G>T		intron_variant, NMD_transcript_variant		4		ENSP00000429149

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000227

AC:

AN:

175970

Hom.:

AF XY:

0.0000323

AC XY:

AN XY:

92880

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000229

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000140

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000213

AC:

AN:

1407706

Hom.:

Cov.:

AF XY:

0.00000288

AC XY:

AN XY:

695330

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000796

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.:

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

Mar 30, 2024

The c.344G>T (p.G115V) alteration is located in exon 3 (coding exon 3) of the KCNU1 gene. This alteration results from a G to T substitution at nucleotide position 344, causing the glycine (G) at amino acid position 115 to be replaced by a valine (V). 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

0.33

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.070

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.61

.;D

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.97

LIST_S2

Pathogenic

0.99

D;D

M_CAP

Benign

0.044

MetaRNN

Uncertain

0.65

D;D

MetaSVM

Benign

-0.51

MutationAssessor

Uncertain

2.6

.;M

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-5.9

D;D

REVEL

Uncertain

0.33

Sift

Uncertain

0.013

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

1.0

.;D

Vest4

0.78

MutPred

0.52

Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);

MVP

0.59

MPC

0.19

ClinPred

0.89

GERP RS

5.2

Varity_R

0.84

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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