Genetic Variant ABHD16B:p.Gln96Pro (chr20-63861827-A-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_080622.4(ABHD16B):c.287A>C(p.Gln96Pro) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000071 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ABHD16B
NM_080622.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.370

Publications

0 publications found

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]

ABHD16B links:

ENSG00000268858 (HGNC:58392):

ENSG00000268858 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.813

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080622.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABHD16B	NM_080622.4	MANE Select	c.287A>C	p.Gln96Pro	missense	Exon 1 of 1	NP_542189.1	Q9H3Z7
ABHD16B-AS1	NR_165198.1		n.2596T>G		non_coding_transcript_exon	Exon 2 of 2
ABHD16B-AS1	NR_165312.1		n.3247T>G		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABHD16B	ENST00000369916.5	TSL:6 MANE Select	c.287A>C	p.Gln96Pro	missense	Exon 1 of 1	ENSP00000358932.3	Q9H3Z7
	ENSG00000268858	ENST00000601296.3	TSL:6	n.3397T>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000706

AC:

AN:

1345016

Hom.:

Cov.:

AF XY:

0.0000588

AC XY:

AN XY:

663296

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000105

AC:

AN:

28668

American (AMR)

AF:

0.0000959

AC:

AN:

31272

Ashkenazi Jewish (ASJ)

AF:

0.000301

AC:

AN:

23238

East Asian (EAS)

AF:

0.000178

AC:

AN:

33644

South Asian (SAS)

AF:

0.0000256

AC:

AN:

78062

European-Finnish (FIN)

AF:

0.000256

AC:

AN:

31288

Middle Eastern (MID)

AF:

0.000207

AC:

AN:

4830

European-Non Finnish (NFE)

AF:

0.0000538

AC:

AN:

1058958

Other (OTH)

AF:

0.000145

AC:

AN:

55056

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.243

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Uncertain

0.045

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.49

M_CAP

Pathogenic

0.58

MetaRNN

Pathogenic

0.81

MetaSVM

Benign

-0.49

MutationAssessor

Uncertain

2.1

PhyloP100

0.37

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-3.9

REVEL

Uncertain

0.30

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.025

Polyphen

0.99

Vest4

0.61

MutPred

0.46

Gain of helix (P = 0.0225)

MVP

0.61

MPC

1.3

ClinPred

0.95

GERP RS

4.4

PromoterAI

-0.012

Neutral

(source)

Varity_R

0.72

gMVP

0.81

Mutation Taster

=74/26

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over