Genetic Variant ANO10:c.-368A>G (chr3-43690699-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001346468.2(ANO10):c.-12+818A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000127 in 236,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

ANO10
NM_001346468.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.101

Publications

0 publications found

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]

ANO10 links:

ABHD5 (HGNC:21396): (abhydrolase domain containing 5, lysophosphatidic acid acyltransferase) The protein encoded by this gene belongs to a large family of proteins defined by an alpha/beta hydrolase fold, and contains three sequence motifs that correspond to a catalytic triad found in the esterase/lipase/thioesterase subfamily. It differs from other members of this subfamily in that its putative catalytic triad contains an asparagine instead of the serine residue. Mutations in this gene have been associated with Chanarin-Dorfman syndrome, a triglyceride storage disease with impaired long-chain fatty acid oxidation. [provided by RefSeq, Jul 2008]

ABHD5 Gene-Disease associations (from GenCC):

Dorfman-Chanarin disease
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ABHD5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346468.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANO10	NM_001346468.2		c.-12+818A>G	intron	N/A	NP_001333397.1	Q9NW15-1
ANO10	NM_001346469.2		c.-12+818A>G	intron	N/A	NP_001333398.1	Q9NW15-3
ABHD5	NM_016006.6	MANE Select	c.-294T>C	upstream_gene	N/A	NP_057090.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANO10	ENST00000910681.1		c.-368A>G	5_prime_UTR_premature_start_codon_gain	Exon 1 of 15	ENSP00000580740.1
ANO10	ENST00000428831.1	TSL:5	c.-190A>G	5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	ENSP00000406712.1	C9IZD0
ANO10	ENST00000436073.1	TSL:4	c.-261A>G	5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000404988.1	C9JJS5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000127

AC:

AN:

236680

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

120966

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

6194

American (AMR)

AF:

0.00

AC:

AN:

6482

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8294

East Asian (EAS)

AF:

0.00

AC:

AN:

20292

South Asian (SAS)

AF:

0.000511

AC:

AN:

5866

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21026

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1186

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

152014

Other (OTH)

AF:

0.00

AC:

AN:

15326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.3

(source)

DANN

Benign

0.48

PhyloP100

0.10

PromoterAI

-0.0024

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over