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GeneBe

8-36815682-A-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001031836.3(KCNU1):c.990A>C(p.Gly330=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,547,638 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0070 ( 21 hom., cov: 32)
Exomes 𝑓: 0.00060 ( 7 hom. )

Consequence

KCNU1
NM_001031836.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.195
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-36815682-A-C is Benign according to our data. Variant chr8-36815682-A-C is described in ClinVar as [Benign]. Clinvar id is 776315.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.195 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.007 (1066/152308) while in subpopulation AFR AF= 0.0243 (1010/41572). AF 95% confidence interval is 0.0231. There are 21 homozygotes in gnomad4. There are 529 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 17 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
KCNU1NM_001031836.3 linkuse as main transcriptc.990A>C p.Gly330= synonymous_variant 9/27 ENST00000399881.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KCNU1ENST00000399881.8 linkuse as main transcriptc.990A>C p.Gly330= synonymous_variant 9/272 NM_001031836.3 P1
KCNU1ENST00000522372.5 linkuse as main transcriptc.990A>C p.Gly330= synonymous_variant, NMD_transcript_variant 9/281

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00693
AC:
1054
AN:
152190
Hom.:
17
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00236
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00669
GnomAD3 exomes
AF:
0.00177
AC:
410
AN:
231620
Hom.:
8
AF XY:
0.00119
AC XY:
150
AN XY:
125958
show subpopulations
Gnomad AFR exome
AF:
0.0254
Gnomad AMR exome
AF:
0.000859
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000376
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000927
Gnomad OTH exome
AF:
0.000885
GnomAD4 exome
AF:
0.000600
AC:
837
AN:
1395330
Hom.:
7
Cov.:
23
AF XY:
0.000518
AC XY:
361
AN XY:
697330
show subpopulations
Gnomad4 AFR exome
AF:
0.0216
Gnomad4 AMR exome
AF:
0.00113
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000490
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000565
Gnomad4 OTH exome
AF:
0.00170
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00700
AC:
1066
AN:
152308
Hom.:
21
Cov.:
32
AF XY:
0.00710
AC XY:
529
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.0243
Gnomad4 AMR
AF:
0.00235
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00662
Alfa
AF:
0.00315
Hom.:
2
Bravo
AF:
0.00763
Asia WGS
AF:
0.00491
AC:
17
AN:
3474
EpiCase
AF:
0.00
EpiControl
AF:
0.0000599

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.64
Cadd
Benign
3.5
Dann
Benign
0.57

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.

Other links and lift over

dbSNP: rs115248021; hg19: chr8-36673200; API