3-43702422-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

10 publications found

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 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

ABHD5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 445947.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABHD5	NM_016006.6 link	c.341G>T	p.Arg114Leu	missense_variant	Exon 3 of 7	ENST00000644371.2	NP_057090.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABHD5	ENST00000644371.2 link	c.341G>T	p.Arg114Leu	missense_variant	Exon 3 of 7		NM_016006.6	ENSP00000495778.1

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

GnomAD2 exomes

AF:

0.00777

AC:

1953

AN:

251474

AF XY:

0.00807

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 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

African (AFR)

AF:

0.00125

AC:

AN:

33480

American (AMR)

AF:

0.00161

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0103

AC:

270

AN:

26134

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39698

South Asian (SAS)

AF:

0.00744

AC:

642

AN:

86258

European-Finnish (FIN)

AF:

0.00751

AC:

401

AN:

53418

Middle Eastern (MID)

AF:

0.00208

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0123

AC:

13726

AN:

1112010

Other (OTH)

AF:

0.00848

AC:

512

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

973

1946

2919

3892

4865

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

516

1032

1548

2064

2580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00722

AC:

1100

AN:

152314

Hom.:

Cov.:

AF XY:

0.00667

AC XY:

497

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.00209

AC:

AN:

41586

American (AMR)

AF:

0.00288

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00692

AC:

AN:

3468

East Asian (EAS)

AF:

0.000386

AC:

AN:

5184

South Asian (SAS)

AF:

0.00477

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00594

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0124

AC:

843

AN:

68032

Other (OTH)

AF:

0.00615

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

113

169

226

282

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0103

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

Feb 14, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ABHD5: BS1, BS2 -

Jun 14, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Triglyceride storage disease with ichthyosis

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

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;.;.;.

PhyloP100

5.1

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

Mutation Taster

=87/13

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over