chr19-1880038-C-A

Variant names:

• chr19-1880038-C-A
• NM_001130111.2:c.410G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001130111.2(ABHD17A):​c.410G>T​(p.Arg137Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABHD17A NM_001130111.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.91

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]

ACMG classification

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, 0.821

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABHD17A	NM_001130111.2	c.410G>T	p.Arg137Leu	missense_variant	Exon 3 of 5	ENST00000292577.12	NP_001123583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABHD17A	ENST00000292577.12	c.410G>T	p.Arg137Leu	missense_variant	Exon 3 of 5	1	NM_001130111.2	ENSP00000292577.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.093	T;.;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D;D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.82	D;D;D
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.8	M;.;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-5.5	D;D;.
REVEL	Uncertain	0.39
Sift	Uncertain	0.013	D;T;.
Sift4G	Benign	0.17	T;T;D
Polyphen		1.0	D;D;.
Vest4		0.92
MutPred		0.57		Loss of methylation at R137 (P = 0.0339);.;.;
MVP		0.72
ClinPred		0.98	D
GERP RS		4.4
Varity_R		0.79
gMVP		0.80

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-1880037; COSMIC: COSV51751523; COSMIC: COSV51751523;