18-21702399-G-C

Position:

• chr18-21702399-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_138340.5(ABHD3):​c.426C>G​(p.Ile142Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABHD3 NM_138340.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.12

Genes affected

ABHD3 (HGNC:18718): (abhydrolase domain containing 3, phospholipase) This gene encodes a protein containing an alpha/beta hydrolase fold, which is a catalytic domain found in a very wide range of enzymes. The function of this protein has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABHD3	NM_138340.5	c.426C>G	p.Ile142Met	missense_variant	3/9	ENST00000289119.7	NP_612213.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABHD3	ENST00000289119.7	c.426C>G	p.Ile142Met	missense_variant	3/9	1	NM_138340.5	ENSP00000289119	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 19, 2024

The c.426C>G (p.I142M) alteration is located in exon 3 (coding exon 3) of the ABHD3 gene. This alteration results from a C to G substitution at nucleotide position 426, causing the isoleucine (I) at amino acid position 142 to be replaced by a methionine (M). 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	0.23
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	19
DANN	Benign	0.71
DEOGEN2	Benign	0.082	T;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Uncertain	0.093	D
MetaRNN	Uncertain	0.58	D;D
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.5	L;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.1	N;.
REVEL	Uncertain	0.35
Sift	Uncertain	0.0020	D;.
Sift4G	Uncertain	0.0030	D;D
Polyphen		0.019	B;.
Vest4		0.67
MutPred		0.60		Gain of glycosylation at P140 (P = 0.1312);Gain of glycosylation at P140 (P = 0.1312);
MVP		0.70
MPC		0.57
ClinPred		0.68	D
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.29
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr18-19282360;