chr2-27309924-T-C

Position:

• chr2-27309924-T-C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_002437.5(MPV17):​c.519A>G​(p.Ala173Ala) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MPV17 NM_002437.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.21

Genes affected

MPV17 (HGNC:7224): (mitochondrial inner membrane protein MPV17) This gene encodes a mitochondrial inner membrane protein that is implicated in the metabolism of reactive oxygen species. Mutations in this gene have been associated with the hepatocerebral form of mitochondrial DNA depletion syndrome (MDDS). [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07315031).
• BP6: Variant 2-27309924-T-C is Benign according to our data. Variant chr2-27309924-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1665671.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.21 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPV17	NM_002437.5	c.519A>G	p.Ala173Ala	synonymous_variant	8/8	ENST00000380044.6	NP_002428.1
MPV17	XM_005264326.5	c.519A>G	p.Ala173Ala	synonymous_variant	8/8		XP_005264383.1
MPV17	XM_017004151.2	c.471A>G	p.Ala157Ala	synonymous_variant	8/8		XP_016859640.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPV17	ENST00000380044.6	c.519A>G	p.Ala173Ala	synonymous_variant	8/8	1	NM_002437.5	ENSP00000369383.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 24, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	4.8
DANN	Benign	0.94
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.31	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-0.98	T
PROVEAN	Benign	0.55	N
REVEL	Benign	0.22
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.062	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.48		Loss of sheet (P = 0.0126);
MVP		0.32
ClinPred		0.047	T
GERP RS		-5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: chr2-27532792;