Variant 18-21651601-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138340.5(ABHD3):c.1220A>T(p.Glu407Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 1,614,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

ABHD3
NM_138340.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.32

Variant links:

Genes affected

ABHD3 (HGNC:18718): (abhydrolase domain containing 3, phospholipase) This gene encodes a protein containing an alpha/beta hydrolase fold, which is a catalytic domain found in a very wide range of enzymes. The function of this protein has not been determined. [provided by RefSeq, Jul 2008]

ABHD3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20942938).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ABHD3	NM_138340.5 linkuse as main transcript	c.1220A>T	p.Glu407Val	missense_variant	9/9	ENST00000289119.7	NP_612213.2
ABHD3	NM_001308256.2 linkuse as main transcript	c.1061A>T	p.Glu354Val	missense_variant	7/7		NP_001295185.1
ABHD3	NM_001308257.2 linkuse as main transcript	c.635A>T	p.Glu212Val	missense_variant	5/5		NP_001295186.1
ABHD3	XM_017025574.2 linkuse as main transcript	c.635A>T	p.Glu212Val	missense_variant	6/6		XP_016881063.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABHD3	ENST00000289119.7 linkuse as main transcript	c.1220A>T	p.Glu407Val	missense_variant	9/9	1	NM_138340.5	ENSP00000289119	P1	Q8WU67-1
ABHD3	ENST00000580981.5 linkuse as main transcript	c.1061A>T	p.Glu354Val	missense_variant	7/7	5		ENSP00000462935
ABHD3	ENST00000578270.5 linkuse as main transcript	c.635A>T	p.Glu212Val	missense_variant	8/8	5		ENSP00000462578

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251376

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000376

AC:

AN:

1461810

Hom.:

Cov.:

AF XY:

0.0000426

AC XY:

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000450

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 21, 2022

The c.1220A>T (p.E407V) alteration is located in exon 9 (coding exon 9) of the ABHD3 gene. This alteration results from a A to T substitution at nucleotide position 1220, causing the glutamic acid (E) at amino acid position 407 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Benign

0.94

DEOGEN2

Benign

0.20

T;.;T

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.80

T;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

M;.;.

MutationTaster

Benign

0.98

D;D;D

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.8

D;.;.

REVEL

Benign

0.074

Sift

Uncertain

0.015

D;.;.

Sift4G

Uncertain

0.022

D;D;D

Polyphen

0.85

P;.;.

Vest4

0.20

MVP

0.41

MPC

0.34

ClinPred

0.67

GERP RS

5.6

Varity_R

0.27

gMVP

0.62

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

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