3-58256689-A-C

Position:

• chr3-58256689-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001320126.2(ABHD6):​c.103A>C​(p.Ile35Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABHD6 NM_001320126.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.04

Genes affected

ABHD6 (HGNC:21398): (abhydrolase domain containing 6, acylglycerol lipase) Enables acylglycerol lipase activity. Involved in acylglycerol catabolic process. Predicted to be located in late endosome membrane and lysosomal membrane. Predicted to be integral component of membrane. Predicted to be part of AMPA glutamate receptor complex. Predicted to be active in GABA-ergic synapse; glutamatergic synapse; and mitochondrion. Predicted to be integral component of postsynaptic membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32252663).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABHD6	NM_001320126.2	c.103A>C	p.Ile35Leu	missense_variant	3/10	ENST00000478253.6	NP_001307055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABHD6	ENST00000478253.6	c.103A>C	p.Ile35Leu	missense_variant	3/10	2	NM_001320126.2	ENSP00000420315.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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

Nov 30, 2022

The c.103A>C (p.I35L) alteration is located in exon 2 (coding exon 1) of the ABHD6 gene. This alteration results from a A to C substitution at nucleotide position 103, causing the isoleucine (I) at amino acid position 35 to be replaced by a leucine (L). 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	0.17
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.11	T;T;T;T
Eigen	Benign	-0.076
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.82	.;T;T;T
M_CAP	Benign	0.075	D
MetaRNN	Benign	0.32	T;T;T;T
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Benign	1.5	L;L;.;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.19	N;N;N;N
REVEL	Uncertain	0.32
Sift	Benign	0.18	T;T;T;T
Sift4G	Benign	0.51	T;T;T;T
Polyphen		0.0020	B;B;.;.
Vest4		0.70
MutPred		0.39		Loss of catalytic residue at I35 (P = 0.0281);Loss of catalytic residue at I35 (P = 0.0281);Loss of catalytic residue at I35 (P = 0.0281);Loss of catalytic residue at I35 (P = 0.0281);
MVP		0.84
MPC		0.20
ClinPred		0.74	D
GERP RS		5.7
Varity_R		0.23
gMVP		0.61

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: chr3-58242416;