chr3-111979112-C-A

Position:

• chr3-111979112-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The ENST00000273359.8(ABHD10):​c.51C>A​(p.Ser17Arg) 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 benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ABHD10 ENST00000273359.8 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0430

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 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=0.07849857).
• BP6: Variant 3-111979112-C-A is Benign according to our data. Variant chr3-111979112-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2251042.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABHD10	NM_018394.4	c.51C>A	p.Ser17Arg	missense_variant	1/5	ENST00000273359.8	NP_060864.1
ABHD10	NM_001272069.2	c.51C>A	p.Ser17Arg	missense_variant	1/6		NP_001258998.1
ABHD10	NR_073570.2	n.87C>A		non_coding_transcript_exon_variant	1/4
ABHD10	NR_073571.2	n.87C>A		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABHD10	ENST00000273359.8	c.51C>A	p.Ser17Arg	missense_variant	1/5	1	NM_018394.4	ENSP00000273359	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 17, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	12
DANN	Benign	0.88
DEOGEN2	Benign	0.0025	T;.
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.61	T;T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.078	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.33	N;N
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.050	N;N
REVEL	Benign	0.070
Sift	Benign	0.99	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.19
MutPred		0.36		Gain of MoRF binding (P = 0.0298);Gain of MoRF binding (P = 0.0298);
MVP		0.29
MPC		0.17
ClinPred		0.11	T
GERP RS		0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.069
gMVP		0.62

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: chr3-111697959;