3-43705505-G-A

Variant names:

• chr3-43705505-G-A
• rs3774793
• NM_016006.6:c.506+2918G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016006.6(ABHD5):​c.506+2918G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0859 in 152,206 control chromosomes in the GnomAD database, including 776 homozygotes. 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: 𝑓 0.086 (776 hom., cov: 32)
• Consequence: ABHD5 NM_016006.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.250
• Publications: 1 publications found

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]

ABHD5 Gene-Disease associations (from GenCC):

• Dorfman-Chanarin disease

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016006.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABHD5	NM_016006.6	MANE Select	c.506+2918G>A		intron	N/A	NP_057090.2
	ABHD5	NM_001355186.2		c.506+2918G>A		intron	N/A	NP_001342115.1
	ABHD5	NM_001365649.1		c.383+2918G>A		intron	N/A	NP_001352578.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABHD5	ENST00000644371.2	MANE Select	c.506+2918G>A		intron	N/A	ENSP00000495778.1
	ABHD5	ENST00000458276.7	TSL:1	c.506+2918G>A		intron	N/A	ENSP00000390849.3
	ABHD5	ENST00000454293.2	TSL:3	c.383+2918G>A		intron	N/A	ENSP00000412014.2

Frequencies

GnomAD3 genomes AF: 0.0856 AC: 13022 AN: 152088 Hom.: 766 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0877

Gnomad ASJ AF: 0.0524

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.0176

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.0491

Gnomad OTH AF: 0.0893

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0859 AC: 13067 AN: 152206 Hom.: 776 Cov.: 32 AF XY: 0.0860 AC XY: 6401 AN XY: 74422

African (AFR) AF: 0.145 AC: 6027 AN: 41510

American (AMR) AF: 0.0875 AC: 1338 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0524 AC: 182 AN: 3472

East Asian (EAS) AF: 0.143 AC: 740 AN: 5182

South Asian (SAS) AF: 0.214 AC: 1032 AN: 4822

European-Finnish (FIN) AF: 0.0176 AC: 186 AN: 10588

Middle Eastern (MID) AF: 0.106 AC: 31 AN: 292

European-Non Finnish (NFE) AF: 0.0491 AC: 3338 AN: 68018

Other (OTH) AF: 0.0912 AC: 193 AN: 2116

Alfa AF: 0.0676 Hom.: 68

Bravo AF: 0.0914

Asia WGS AF: 0.183 AC: 632 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.0
DANN	Benign	0.69
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3774793; hg19: chr3-43746997;