19-1880946-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_031213.4(ABHD17A):​c.435C>A​(p.Ser145Arg) 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. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Consequence

ABHD17A
NM_031213.4 missense

Scores

15

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.11
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.056376755).
BP6
Variant 19-1880946-G-T is Benign according to our data. Variant chr19-1880946-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2491537.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ABHD17ANM_001130111.2 linkc.332+289C>A intron_variant ENST00000292577.12 NP_001123583.1 Q96GS6-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ABHD17AENST00000292577.12 linkc.332+289C>A intron_variant 1 NM_001130111.2 ENSP00000292577.6 Q96GS6-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsFeb 28, 2023This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.75
CADD
Benign
0.32
DANN
Benign
0.49
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.0047
N
LIST_S2
Benign
0.20
T
M_CAP
Benign
0.0016
T
MetaRNN
Benign
0.056
T
MetaSVM
Benign
-0.99
T
PROVEAN
Benign
-0.070
N
REVEL
Benign
0.038
Sift
Benign
0.29
T
Sift4G
Benign
0.59
T
Polyphen
0.0
B
Vest4
0.082
MutPred
0.44
Loss of ubiquitination at K144 (P = 0.0738);
MVP
0.11
ClinPred
0.40
T
GERP RS
-2.7
gMVP
0.75

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: chr19-1880945; API