3-111979196-G-T

Position:

• chr3-111979196-G-T

Variant summary

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

The ENST00000273359.8(ABHD10):​c.135G>T​(p.Trp45Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ABHD10 ENST00000273359.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.11

Genes affected

ABHD10 (HGNC:25656): (abhydrolase domain containing 10, depalmitoylase) This gene encodes a mitochondrially-localized enzyme that acts in liver cells as a hydrolase. The encoded protein removes glucuronide from mycophenolic acid acyl-glucuronide. There is a pseudogene for this gene on chromosome 6. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

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
ABHD10	NM_018394.4	c.135G>T	p.Trp45Cys	missense_variant	1/5	ENST00000273359.8	NP_060864.1
ABHD10	NM_001272069.2	c.135G>T	p.Trp45Cys	missense_variant	1/6		NP_001258998.1
ABHD10	NR_073570.2	n.171G>T		non_coding_transcript_exon_variant	1/4
ABHD10	NR_073571.2	n.171G>T		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABHD10	ENST00000273359.8	c.135G>T	p.Trp45Cys	missense_variant	1/5	1	NM_018394.4	ENSP00000273359	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1450824 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 720368

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Jun 10, 2024

The c.135G>T (p.W45C) alteration is located in exon 1 (coding exon 1) of the ABHD10 gene. This alteration results from a G to T substitution at nucleotide position 135, causing the tryptophan (W) at amino acid position 45 to be replaced by a cysteine (C). 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	0.21
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.16	T;.
Eigen	Benign	0.076
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.64	T;T
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.64	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.11
Sift	Benign	0.11	T;D
Sift4G	Benign	0.10	T;T
Polyphen		0.69	P;.
Vest4		0.56
MutPred		0.57		Loss of MoRF binding (P = 0.0076);Loss of MoRF binding (P = 0.0076);
MVP		0.51
MPC		0.56
ClinPred		0.94	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.16
gMVP		0.69

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: chr3-111698043;