chr19-1880974-G-T

Variant names:

• chr19-1880974-G-T
• rs746433957
• ENST00000250974.9:c.407C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031213.4(ABHD17A):​c.407C>A​(p.Ala136Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A136G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: ABHD17A NM_031213.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.25
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0868887).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031213.4. 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.332+261C>A		intron	N/A	NP_001123583.1	Q96GS6-1
	ABHD17A	NM_031213.4		c.407C>A	p.Ala136Glu	missense	Exon 3 of 6	NP_112490.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABHD17A	ENST00000250974.9	TSL:1	c.407C>A	p.Ala136Glu	missense	Exon 3 of 6	ENSP00000250974.9	Q96GS6-2
	ABHD17A	ENST00000292577.12	TSL:1 MANE Select	c.332+261C>A		intron	N/A	ENSP00000292577.6	Q96GS6-1
	ABHD17A	ENST00000590661.1	TSL:1	c.332+261C>A		intron	N/A	ENSP00000467638.1	K7EQ25

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.27
DANN	Benign	0.83
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-1.0	T
PhyloP100		-4.2
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.12
Sift	Benign	0.090	T
Sift4G	Benign	0.29	T
Polyphen		0.54	P
Vest4		0.14
MutPred		0.41		Gain of solvent accessibility (P = 0.0145)
MVP		0.18
ClinPred		0.46	T
GERP RS		-3.2
gMVP		0.55
Mutation Taster		=99/1	polymorphism

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: rs746433957; hg19: chr19-1880973;