ENST00000910681.1:c.-368A>T

Variant names:

• chr3-43690699-T-A
• rs79739454
• ENST00000910681.1:c.-368A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000910681.1(ANO10):​c.-368A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0231 in 388,780 control chromosomes in the GnomAD database, including 156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (60 hom., cov: 32)
  • Exomes 𝑓: 0.023 (96 hom.)
• Consequence: ANO10 ENST00000910681.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.101
• Publications: 1 publications found

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]

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)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 3-43690699-T-A is Benign according to our data. Variant chr3-43690699-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 673914.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0845 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000910681.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.0225 AC: 3425 AN: 152200 Hom.: 58 Cov.: 32

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0234

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.0276

Gnomad SAS AF: 0.0915

Gnomad FIN AF: 0.00499

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0255

Gnomad OTH AF: 0.0273

GnomAD4 exome AF: 0.0235 AC: 5556 AN: 236462 Hom.: 96 Cov.: 0 AF XY: 0.0241 AC XY: 2908 AN XY: 120842

African (AFR) AF: 0.0123 AC: 76 AN: 6192

American (AMR) AF: 0.0370 AC: 240 AN: 6480

Ashkenazi Jewish (ASJ) AF: 0.0299 AC: 248 AN: 8288

East Asian (EAS) AF: 0.0306 AC: 621 AN: 20284

South Asian (SAS) AF: 0.0568 AC: 332 AN: 5848

European-Finnish (FIN) AF: 0.00628 AC: 132 AN: 21018

Middle Eastern (MID) AF: 0.0491 AC: 58 AN: 1182

European-Non Finnish (NFE) AF: 0.0229 AC: 3470 AN: 151858

Other (OTH) AF: 0.0248 AC: 379 AN: 15312

GnomAD4 genome AF: 0.0226 AC: 3435 AN: 152318 Hom.: 60 Cov.: 32 AF XY: 0.0226 AC XY: 1680 AN XY: 74496

African (AFR) AF: 0.0131 AC: 545 AN: 41590

American (AMR) AF: 0.0234 AC: 358 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0268 AC: 93 AN: 3468

East Asian (EAS) AF: 0.0273 AC: 141 AN: 5164

South Asian (SAS) AF: 0.0915 AC: 442 AN: 4828

European-Finnish (FIN) AF: 0.00499 AC: 53 AN: 10626

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0255 AC: 1736 AN: 68016

Other (OTH) AF: 0.0270 AC: 57 AN: 2112

Alfa AF: 0.0218 Hom.: 7

Bravo AF: 0.0218

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.54
PhyloP100		0.10
PromoterAI		0.057	Neutral

Splicing

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

Other links and lift over

dbSNP: rs79739454; hg19: chr3-43732191;