8-36787341-T-G

Variant names:

• chr8-36787341-T-G
• rs374074583
• NM_001031836.3:c.231T>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001031836.3(KCNU1):​c.231T>G​(p.His77Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/24 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KCNU1 NM_001031836.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.441

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNU1	NM_001031836.3	c.231T>G	p.His77Gln	missense_variant	Exon 2 of 27	ENST00000399881.8	NP_001027006.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNU1	ENST00000399881.8	c.231T>G	p.His77Gln	missense_variant	Exon 2 of 27	2	NM_001031836.3	ENSP00000382770.3
KCNU1	ENST00000522372.5	n.231T>G		non_coding_transcript_exon_variant	Exon 2 of 28	1		ENSP00000428552.1
KCNU1	ENST00000523973.5	c.231T>G	p.His77Gln	missense_variant	Exon 2 of 8	5		ENSP00000429951.1
KCNU1	ENST00000522417.1	n.231T>G		non_coding_transcript_exon_variant	Exon 2 of 5	4		ENSP00000429149.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.3
DANN	Benign	0.57
DEOGEN2	Benign	0.025	.;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.24	T;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.082	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.84	.;L
PhyloP100		-0.44
PrimateAI	Benign	0.28	T
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		0.060	T
GERP RS		-5.3
Varity_R		0.033
gMVP		0.043
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.56		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.56		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Loading publications...

Other links and lift over

dbSNP: rs374074583; hg19: chr8-36644859;