chr3-43366831-A-AC

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting

The NM_018075.5(ANO10):​c.*74_*75insG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000149 in 1,438,650 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

ANO10
NM_018075.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.104
Variant links:
Genes affected
ANO10 (HGNC:25519): (anoctamin 10) The transmembrane protein encoded by this gene belongs to the anoctamin family of calcium-activated chloride channels, also known as the transmembrane 16 family. The encoded protein contains eight transmembrane domains with cytosolic N- and C-termini. Defects in this gene may cause autosomal recessive spinocerebellar ataxia-10. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]
SNRK (HGNC:30598): (SNF related kinase) SNRK is a member of the sucrose nonfermenting (SNF)-related kinase family of serine/threonine kinases (Kertesz et al., 2002 [PubMed 12234663]).[supplied by OMIM, Apr 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000172 (26/151600) while in subpopulation EAS AF= 0.00291 (15/5146). AF 95% confidence interval is 0.0018. There are 0 homozygotes in gnomad4. There are 13 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ANO10NM_018075.5 linkuse as main transcriptc.*74_*75insG 3_prime_UTR_variant 13/13 ENST00000292246.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ANO10ENST00000292246.8 linkuse as main transcriptc.*74_*75insG 3_prime_UTR_variant 13/131 NM_018075.5 P1Q9NW15-1

Frequencies

GnomAD3 genomes
AF:
0.000172
AC:
26
AN:
151488
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00291
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000884
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.000146
AC:
188
AN:
1287050
Hom.:
0
Cov.:
21
AF XY:
0.000147
AC XY:
94
AN XY:
640468
show subpopulations
Gnomad4 AFR exome
AF:
0.0000342
Gnomad4 AMR exome
AF:
0.0000281
Gnomad4 ASJ exome
AF:
0.0000408
Gnomad4 EAS exome
AF:
0.00218
Gnomad4 SAS exome
AF:
0.000156
Gnomad4 FIN exome
AF:
0.0000206
Gnomad4 NFE exome
AF:
0.0000848
Gnomad4 OTH exome
AF:
0.000202
GnomAD4 genome
AF:
0.000172
AC:
26
AN:
151600
Hom.:
0
Cov.:
32
AF XY:
0.000175
AC XY:
13
AN XY:
74106
show subpopulations
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00291
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000884
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000174
Asia WGS
AF:
0.00115
AC:
4
AN:
3478

ClinVar

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

Submissions by phenotype

Autosomal recessive cerebellar ataxia Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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: rs556549778; hg19: chr3-43408323; API