20-63861667-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_080622.4(ABHD16B):​c.127C>T​(p.Arg43Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000429 in 1,536,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. R43Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

ABHD16B
NM_080622.4 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.671
Variant links:
Genes affected
ABHD16B (HGNC:16128): (abhydrolase domain containing 16B) Predicted to enable acylglycerol lipase activity; palmitoyl-(protein) hydrolase activity; and phospholipase activity. Predicted to be involved in monoacylglycerol catabolic process and phosphatidylserine catabolic process. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.056010276).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ABHD16BNM_080622.4 linkc.127C>T p.Arg43Trp missense_variant Exon 1 of 1 ENST00000369916.5 NP_542189.1 Q9H3Z7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ABHD16BENST00000369916.5 linkc.127C>T p.Arg43Trp missense_variant Exon 1 of 1 6 NM_080622.4 ENSP00000358932.3 Q9H3Z7
ENSG00000268858ENST00000601296.2 linkn.2627G>A non_coding_transcript_exon_variant Exon 1 of 1 6

Frequencies

GnomAD3 genomes
AF:
0.000112
AC:
17
AN:
151918
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000387
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000869
AC:
12
AN:
138032
Hom.:
0
AF XY:
0.0000803
AC XY:
6
AN XY:
74688
show subpopulations
Gnomad AFR exome
AF:
0.000141
Gnomad AMR exome
AF:
0.000369
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000188
Gnomad OTH exome
AF:
0.000240
GnomAD4 exome
AF:
0.0000354
AC:
49
AN:
1384838
Hom.:
0
Cov.:
32
AF XY:
0.0000439
AC XY:
30
AN XY:
683532
show subpopulations
Gnomad4 AFR exome
AF:
0.000482
Gnomad4 AMR exome
AF:
0.000338
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000566
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.29e-7
Gnomad4 OTH exome
AF:
0.0000173
GnomAD4 genome
AF:
0.000112
AC:
17
AN:
152030
Hom.:
0
Cov.:
31
AF XY:
0.0000807
AC XY:
6
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.000386
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000166
ExAC
AF:
0.0000240
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 27, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.127C>T (p.R43W) alteration is located in exon 1 (coding exon 1) of the ABHD16B gene. This alteration results from a C to T substitution at nucleotide position 127, causing the arginine (R) at amino acid position 43 to be replaced by a tryptophan (W). 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
Benign
0.10
BayesDel_addAF
Benign
-0.55
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
7.9
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0081
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.034
N
LIST_S2
Benign
0.52
T
M_CAP
Benign
0.025
D
MetaRNN
Benign
0.056
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
-1.8
N
REVEL
Benign
0.044
Sift
Uncertain
0.016
D
Sift4G
Uncertain
0.010
D
Polyphen
0.0
B
Vest4
0.23
MutPred
0.36
Loss of disorder (P = 0.0023);
MVP
0.12
MPC
0.68
ClinPred
0.013
T
GERP RS
-2.0
Varity_R
0.037
gMVP
0.25

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: rs370049220; hg19: chr20-62493020; COSMIC: COSV53863387; COSMIC: COSV53863387; API