Genetic Variant ABHD17A:p.Ala168Thr (chr19-1879946-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001130111.2(ABHD17A):c.502G>A(p.Ala168Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000161 in 1,611,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

ABHD17A
NM_001130111.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.74

Variant links:

Genes affected

ABHD17A (HGNC:28756): (abhydrolase domain containing 17A, depalmitoylase) Enables palmitoyl-(protein) hydrolase activity. Involved in protein depalmitoylation and protein localization to membrane. Located in endosome membrane; nuclear speck; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ABHD17A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.802

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABHD17A	NM_001130111.2 link	c.502G>A	p.Ala168Thr	missense_variant	Exon 3 of 5	ENST00000292577.12	NP_001123583.1	Q96GS6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABHD17A	ENST00000292577.12 link	c.502G>A	p.Ala168Thr	missense_variant	Exon 3 of 5	1	NM_001130111.2	ENSP00000292577.6		Q96GS6-1

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000102

AC:

AN:

224638

Hom.:

AF XY:

0.000121

AC XY:

AN XY:

123576

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000312

Gnomad ASJ exome

AF:

0.000316

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000683

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000162

Gnomad OTH exome

AF:

0.000180

GnomAD4 exome

AF:

0.000170

AC:

248

AN:

1459766

Hom.:

Cov.:

AF XY:

0.000172

AC XY:

125

AN XY:

726238

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.000996

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0000192

Gnomad4 NFE exome

AF:

0.000179

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000296

Hom.:

Bravo

AF:

0.0000982

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000238

AC:

ExAC

AF:

0.0000831

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.655G>A (p.A219T) alteration is located in exon 4 (coding exon 3) of the ABHD17A gene. This alteration results from a G to A substitution at nucleotide position 655, causing the alanine (A) at amino acid position 219 to be replaced by a threonine (T). 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

Uncertain

0.37

BayesDel_addAF

Uncertain

0.041

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

T;.;T

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Uncertain

0.10

MetaRNN

Pathogenic

0.80

D;D;D

MetaSVM

Uncertain

-0.28

MutationAssessor

Uncertain

2.7

M;.;.

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-3.2

D;D;.

REVEL

Uncertain

0.39

Sift

Uncertain

0.0010

D;D;.

Sift4G

Uncertain

0.043

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.94

MVP

0.77

ClinPred

0.77

GERP RS

4.5

Varity_R

0.82

gMVP

0.79

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