chr19-1879946-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The ENST00000292577.12(ABHD17A):​c.502G>A​(p.Ala168Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000161 in 1,611,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

ABHD17A
ENST00000292577.12 missense

Scores

3
14
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.74
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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, 0.802

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ABHD17ANM_001130111.2 linkuse as main transcriptc.502G>A p.Ala168Thr missense_variant 3/5 ENST00000292577.12 NP_001123583.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ABHD17AENST00000292577.12 linkuse as main transcriptc.502G>A p.Ala168Thr missense_variant 3/51 NM_001130111.2 ENSP00000292577 P1Q96GS6-1

Frequencies

GnomAD3 genomes
AF:
0.0000788
AC:
12
AN:
152220
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000102
AC:
23
AN:
224638
Hom.:
0
AF XY:
0.000121
AC XY:
15
AN XY:
123576
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000312
Gnomad ASJ exome
AF:
0.000316
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000683
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000162
Gnomad OTH exome
AF:
0.000180
GnomAD4 exome
AF:
0.000170
AC:
248
AN:
1459766
Hom.:
0
Cov.:
31
AF XY:
0.000172
AC XY:
125
AN XY:
726238
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
Gnomad4 AMR exome
AF:
0.0000225
Gnomad4 ASJ exome
AF:
0.000996
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.0000192
Gnomad4 NFE exome
AF:
0.000179
Gnomad4 OTH exome
AF:
0.000265
GnomAD4 genome
AF:
0.0000788
AC:
12
AN:
152220
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74364
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000296
Hom.:
1
Bravo
AF:
0.0000982
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000238
AC:
2
ExAC
AF:
0.0000831
AC:
10

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 22, 2023The c.655G>A (p.A219T) alteration is located in exon 4 (coding exon 3) of the ABHD17A gene. This alteration results from a G to A substitution at nucleotide position 655, causing the alanine (A) at amino acid position 219 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.37
BayesDel_addAF
Uncertain
0.041
T
BayesDel_noAF
Uncertain
0.070
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.15
T;.;T
Eigen
Uncertain
0.48
Eigen_PC
Uncertain
0.33
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.92
D;D;D
M_CAP
Uncertain
0.10
D
MetaRNN
Pathogenic
0.80
D;D;D
MetaSVM
Uncertain
-0.28
T
MutationAssessor
Uncertain
2.7
M;.;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Pathogenic
0.82
D
PROVEAN
Uncertain
-3.2
D;D;.
REVEL
Uncertain
0.39
Sift
Uncertain
0.0010
D;D;.
Sift4G
Uncertain
0.043
D;D;D
Polyphen
1.0
D;D;.
Vest4
0.94
MVP
0.77
ClinPred
0.77
D
GERP RS
4.5
Varity_R
0.82
gMVP
0.79

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs143288952; hg19: chr19-1879945; API