chr19-1881326-G-C

Variant names:

• chr19-1881326-G-C
• rs1191556249
• NM_001130111.2:c.241C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001130111.2(ABHD17A):​c.241C>G​(p.Arg81Gly) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: ABHD17A NM_001130111.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.21
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.772

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130111.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABHD17A	NM_001130111.2	MANE Select	c.241C>G	p.Arg81Gly	missense	Exon 2 of 5	NP_001123583.1	Q96GS6-1
	ABHD17A	NM_031213.4		c.241C>G	p.Arg81Gly	missense	Exon 2 of 6	NP_112490.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABHD17A	ENST00000292577.12	TSL:1 MANE Select	c.241C>G	p.Arg81Gly	missense	Exon 2 of 5	ENSP00000292577.6	Q96GS6-1
	ABHD17A	ENST00000250974.9	TSL:1	c.241C>G	p.Arg81Gly	missense	Exon 2 of 6	ENSP00000250974.9	Q96GS6-2
	ABHD17A	ENST00000590661.1	TSL:1	c.241C>G	p.Arg81Gly	missense	Exon 1 of 4	ENSP00000467638.1	K7EQ25

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.56	T
MutationAssessor	Pathogenic	3.5	M
PhyloP100		5.2
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.039	D
Polyphen		0.77	P
Vest4		0.88
MutPred		0.47		Gain of relative solvent accessibility (P = 0.0275)
MVP		0.68
ClinPred		0.99	D
GERP RS		3.8
PromoterAI		0.0077	Neutral
Varity_R		0.71
gMVP		0.71
Mutation Taster		=27/73	disease causing

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

Other links and lift over

dbSNP: rs1191556249; hg19: chr19-1881325;