chr16-15396018-C-G

Position:

• chr16-15396018-C-G

Variant summary

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

The ENST00000396385.4(MPV17L):​c.121C>G​(p.Arg41Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000218 in 1,375,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: MPV17L ENST00000396385.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.240

Genes affected

MPV17L (HGNC:26827): (MPV17 mitochondrial inner membrane protein like) Involved in negative regulation of hydrogen peroxide biosynthetic process; negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway; and reactive oxygen species metabolic process. Located in peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000261130 (HGNC:):

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=0.081884444).
• BP6: Variant 16-15396018-C-G is Benign according to our data. Variant chr16-15396018-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2610768.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPV17L	NM_001128423.2	c.121C>G	p.Arg41Gly	missense_variant	1/4	ENST00000396385.4	NP_001121895.1
MPV17L-BMERB1	NM_001414674.1	c.121C>G	p.Arg41Gly	missense_variant	1/6		NP_001401603.1
MPV17L	NM_173803.4	c.121C>G	p.Arg41Gly	missense_variant	1/3		NP_776164.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPV17L	ENST00000396385.4	c.121C>G	p.Arg41Gly	missense_variant	1/4	1	NM_001128423.2	ENSP00000379669.3
ENSG00000261130	ENST00000568766.1	c.121C>G	p.Arg41Gly	missense_variant	1/2	2		ENSP00000454340.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000218 AC: 3 AN: 1375544 Hom.: 0 Cov.: 31 AF XY: 0.00000442 AC XY: 3 AN XY: 678318

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: 0.00000186

Gnomad4 OTH exome AF: 0.0000174

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

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

Jul 11, 2023

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	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	0.35
DANN	Benign	0.50
DEOGEN2	Benign	0.029	.;T;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0080	N
LIST_S2	Benign	0.19	T;T;T
M_CAP	Pathogenic	0.40	D
MetaRNN	Benign	0.082	T;T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	-0.92	N;N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Uncertain	0.39
Sift	Benign	0.40	T;T;T
Sift4G	Benign	0.55	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.086
MutPred		0.46		Loss of MoRF binding (P = 0.045);Loss of MoRF binding (P = 0.045);Loss of MoRF binding (P = 0.045);
MVP		0.41
MPC		1.8
ClinPred		0.039	T
GERP RS		-1.4
Varity_R		0.048
gMVP		0.58

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

LitVar

Other links and lift over

dbSNP: rs773663453; hg19: chr16-15489875;