3-43690879-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001365650.1(ABHD5):c.-114A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0609 in 1,189,234 control chromosomes in the GnomAD database, including 3,382 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.084 (742 hom., cov: 32)
  • Exomes 𝑓: 0.058 (2640 hom.)
• Consequence: ABHD5 NM_001365650.1 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.94

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 3-43690879-A-G is Benign according to our data. Variant chr3-43690879-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 369420.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABHD5	NM_001365650.1	c.-114A>G		5_prime_UTR_variant	1/6
ABHD5	XM_047448243.1	c.-114A>G		5_prime_UTR_variant	1/8
ANO10	NM_001346468.2	c.-12+638T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANO10	ENST00000413397.5	c.-12+638T>C		intron_variant		4
ANO10	ENST00000439141.5	c.-106+638T>C		intron_variant		4
ABHD5	ENST00000456453.5	c.-77+169A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0837 AC: 12706 AN: 151894 Hom.: 730 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0874

Gnomad ASJ AF: 0.0525

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.0175

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.0490

Gnomad OTH AF: 0.0881

GnomAD4 exome AF: 0.0575 AC: 59643 AN: 1037228 Hom.: 2640 Cov.: 13 AF XY: 0.0605 AC XY: 30934 AN XY: 511224

Gnomad4 AFR exome AF: 0.142

Gnomad4 AMR exome AF: 0.101

Gnomad4 ASJ exome AF: 0.0484

Gnomad4 EAS exome AF: 0.169

Gnomad4 SAS exome AF: 0.186

Gnomad4 FIN exome AF: 0.0203

Gnomad4 NFE exome AF: 0.0440

Gnomad4 OTH exome AF: 0.0730

GnomAD4 genome AF: 0.0839 AC: 12753 AN: 152006 Hom.: 742 Cov.: 32 AF XY: 0.0842 AC XY: 6259 AN XY: 74310

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.0872

Gnomad4 ASJ AF: 0.0525

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.0175

Gnomad4 NFE AF: 0.0490

Gnomad4 OTH AF: 0.0900

Alfa AF: 0.0635 Hom.: 61

Bravo AF: 0.0895

Asia WGS AF: 0.180 AC: 621 AN: 3472

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Triglyceride storage disease with ichthyosis Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	1.6
Dann	Benign	0.42

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

Other links and lift over

dbSNP: rs74845403; hg19: chr3-43732371;