chr8-36808788-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001031836.3(KCNU1):c.727C>T(p.His243Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
KCNU1
NM_001031836.3 missense
NM_001031836.3 missense
Scores
6
6
5
Clinical Significance
Conservation
PhyloP100: 7.04
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.887
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNU1 | NM_001031836.3 | c.727C>T | p.His243Tyr | missense_variant | 7/27 | ENST00000399881.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNU1 | ENST00000399881.8 | c.727C>T | p.His243Tyr | missense_variant | 7/27 | 2 | NM_001031836.3 | P1 | |
KCNU1 | ENST00000522372.5 | c.727C>T | p.His243Tyr | missense_variant, NMD_transcript_variant | 7/28 | 1 | |||
KCNU1 | ENST00000523973.5 | c.727C>T | p.His243Tyr | missense_variant | 7/8 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 29
GnomAD4 exome
Cov.:
29
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
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 | Feb 03, 2022 | The c.727C>T (p.H243Y) alteration is located in exon 7 (coding exon 7) of the KCNU1 gene. This alteration results from a C to T substitution at nucleotide position 727, causing the histidine (H) at amino acid position 243 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Benign
T;D
Sift4G
Benign
T;D
Polyphen
1.0
.;D
Vest4
0.75
MutPred
Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);
MVP
MPC
0.19
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.