Variant 4-128028502-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001358451.3(ABHD18):c.829T>A(p.Phe277Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000042 in 1,427,938 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: not found (cov: 33)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

ABHD18
NM_001358451.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.55

Variant links:

Genes affected

ABHD18 (HGNC:26111): (abhydrolase domain containing 18) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ABHD18 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.951

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABHD18	NM_001358451.3 linkuse as main transcript	c.829T>A	p.Phe277Ile	missense_variant	11/13	ENST00000645843.2	NP_001345380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ABHD18	ENST00000645843.2 linkuse as main transcript	c.829T>A	p.Phe277Ile	missense_variant	11/13		NM_001358451.3	ENSP00000496010.1	A0A2R8YEZ0
ABHD18	ENST00000444616.5 linkuse as main transcript	c.727T>A	p.Phe243Ile	missense_variant	10/11	5		ENSP00000397229.1	Q0P651-1
ABHD18	ENST00000388795.10 linkuse as main transcript	n.*587T>A		non_coding_transcript_exon_variant	11/13	5		ENSP00000373447.6	B7WP89
ABHD18	ENST00000388795.10 linkuse as main transcript	n.*587T>A		3_prime_UTR_variant	11/13	5		ENSP00000373447.6	B7WP89

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000934

AC:

AN:

214218

Hom.:

AF XY:

0.00000860

AC XY:

AN XY:

116284

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000201

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000420

AC:

AN:

1427938

Hom.:

Cov.:

AF XY:

0.00000423

AC XY:

AN XY:

708432

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000546

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000628

Hom.:

Bravo

AF:

0.00000378

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

Dec 09, 2023

The c.727T>A (p.F243I) alteration is located in exon 10 (coding exon 9) of the ABHD18 gene. This alteration results from a T to A substitution at nucleotide position 727, causing the phenylalanine (F) at amino acid position 243 to be replaced by an isoleucine (I). 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

0.31

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.060

T;.;T;T;.

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.84

T;D;.;D;D

M_CAP

Benign

0.015

MetaRNN

Pathogenic

0.95

D;D;D;D;D

MetaSVM

Benign

-0.36

PROVEAN

Uncertain

-4.1

D;.;D;D;.

REVEL

Pathogenic

0.80

Sift

Uncertain

0.014

D;.;D;T;.

Sift4G

Uncertain

0.020

D;.;D;D;D

Polyphen

0.91

P;.;P;D;.

Vest4

0.63

MutPred

0.85

Loss of ubiquitination at K238 (P = 0.0736);.;Loss of ubiquitination at K238 (P = 0.0736);.;.;

MVP

0.39

MPC

0.40

ClinPred

0.96

GERP RS

3.3

Varity_R

0.29

gMVP

0.72

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