3-43702422-G-T

Position:

chr3-43702422-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_016006.6(ABHD5):c.341G>T(p.Arg114Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0104 in 1,614,200 control chromosomes in the GnomAD database, including 131 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0072 ( 5 hom., cov: 32)

Exomes 𝑓: 0.011 ( 126 hom. )

Consequence

ABHD5
NM_016006.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 5.10

Variant links:

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 links:

ABHD5 (HGNC:):

ABHD5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.023979723).

BP6

Variant 3-43702422-G-T is Benign according to our data. Variant chr3-43702422-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 445947.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-43702422-G-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00722 (1100/152314) while in subpopulation NFE AF= 0.0124 (843/68032). AF 95% confidence interval is 0.0117. There are 5 homozygotes in gnomad4. There are 497 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABHD5	NM_016006.6 linkuse as main transcript	c.341G>T	p.Arg114Leu	missense_variant	3/7	ENST00000644371.2	NP_057090.2	Q8WTS1A0A0S2Z5D6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABHD5	ENST00000644371.2 linkuse as main transcript	c.341G>T	p.Arg114Leu	missense_variant	3/7		NM_016006.6	ENSP00000495778.1		Q8WTS1

Frequencies

GnomAD3 genomes

AF:

0.00723

AC:

1100

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00210

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.00692

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00477

Gnomad FIN

AF:

0.00594

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0124

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00777

AC:

1953

AN:

251474

Hom.:

AF XY:

0.00807

AC XY:

1097

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00168

Gnomad ASJ exome

AF:

0.00893

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00719

Gnomad FIN exome

AF:

0.00647

Gnomad NFE exome

AF:

0.0120

Gnomad OTH exome

AF:

0.00912

GnomAD4 exome

AF:

0.0107

AC:

15679

AN:

1461886

Hom.:

126

Cov.:

AF XY:

0.0106

AC XY:

7745

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00125

Gnomad4 AMR exome

AF:

0.00161

Gnomad4 ASJ exome

AF:

0.0103

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00744

Gnomad4 FIN exome

AF:

0.00751

Gnomad4 NFE exome

AF:

0.0123

Gnomad4 OTH exome

AF:

0.00848

GnomAD4 genome

AF:

0.00722

AC:

1100

AN:

152314

Hom.:

Cov.:

AF XY:

0.00667

AC XY:

497

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00209

Gnomad4 AMR

AF:

0.00288

Gnomad4 ASJ

AF:

0.00692

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00477

Gnomad4 FIN

AF:

0.00594

Gnomad4 NFE

AF:

0.0124

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.0105

Hom.:

Bravo

AF:

0.00668

TwinsUK

AF:

0.0127

AC:

ALSPAC

AF:

0.0130

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.0131

AC:

113

ExAC

AF:

0.00829

AC:

1006

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0109

EpiControl

AF:

0.0106

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jun 14, 2017	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	ABHD5: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 14, 2021	- -

Triglyceride storage disease with ichthyosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.44

.;T;.;.;.

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.96

D;.;D;.;D

MetaRNN

Benign

0.024

T;T;T;T;T

MetaSVM

Uncertain

0.071

MutationAssessor

Benign

2.0

.;M;.;.;.

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-6.4

D;.;D;.;.

REVEL

Uncertain

0.60

Sift

Uncertain

0.0010

D;.;D;.;.

Sift4G

Pathogenic

0.0010

D;.;D;.;.

Polyphen

1.0

.;D;.;.;.

Vest4

0.72

MVP

0.87

MPC

0.61

ClinPred

0.035

GERP RS

4.0

Varity_R

0.60

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over