19-1880974-G-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_031213.4(ABHD17A):​c.407C>T​(p.Ala136Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000775 in 1,612,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). 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: 𝑓 0.000079 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000077 (0 hom.)
• Consequence: ABHD17A NM_031213.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.019993067).

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>T		intron	N/A	NP_001123583.1	Q96GS6-1
	ABHD17A	NM_031213.4		c.407C>T	p.Ala136Val	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>T	p.Ala136Val	missense	Exon 3 of 6	ENSP00000250974.9	Q96GS6-2
	ABHD17A	ENST00000292577.12	TSL:1 MANE Select	c.332+261C>T		intron	N/A	ENSP00000292577.6	Q96GS6-1
	ABHD17A	ENST00000590661.1	TSL:1	c.332+261C>T		intron	N/A	ENSP00000467638.1	K7EQ25

Frequencies

GnomAD3 genomes AF: 0.0000788 AC: 12 AN: 152258 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000137 AC: 34 AN: 248092 AF XY: 0.000104

Gnomad AFR exome AF: 0.0000627

Gnomad AMR exome AF: 0.000638

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000985

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000774 AC: 113 AN: 1460178 Hom.: 0 Cov.: 35 AF XY: 0.0000675 AC XY: 49 AN XY: 726450

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.000649 AC: 29 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26108

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52322

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000675 AC: 75 AN: 1111566

Other (OTH) AF: 0.000116 AC: 7 AN: 60328

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152258 Hom.: 0 Cov.: 34 AF XY: 0.0000672 AC XY: 5 AN XY: 74380

African (AFR) AF: 0.0000723 AC: 3 AN: 41474

American (AMR) AF: 0.000196 AC: 3 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000869

ExAC AF: 0.000107 AC: 13

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

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	Benign	0.093
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.88
DANN	Benign	0.96
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.020	T
MetaSVM	Benign	-1.1	T
PhyloP100		-4.2
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.042
Sift	Benign	1.0	T
Sift4G	Benign	0.26	T
Polyphen		0.0020	B
Vest4		0.11
MutPred		0.30		Loss of disorder (P = 0.0682)
MVP		0.14
ClinPred		0.15	T
GERP RS		-3.2
gMVP		0.35
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; COSMIC: COSV99171282; COSMIC: COSV99171282;