Variant 16-15396168-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001128423.2(MPV17L):c.271G>T(p.Val91Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000245 in 1,550,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

MPV17L
NM_001128423.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00500

Variant links:

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]

MPV17L links:

MPV17L-BMERB1 (HGNC:):

MPV17L-BMERB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.045357138).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MPV17L	NM_001128423.2 linkuse as main transcript	c.271G>T	p.Val91Leu	missense_variant	1/4	ENST00000396385.4	NP_001121895.1
MPV17L-BMERB1	NM_001414674.1 linkuse as main transcript	c.271G>T	p.Val91Leu	missense_variant	1/6		NP_001401603.1
MPV17L	NM_173803.4 linkuse as main transcript	c.271G>T	p.Val91Leu	missense_variant	1/3		NP_776164.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPV17L	ENST00000396385.4 linkuse as main transcript	c.271G>T	p.Val91Leu	missense_variant	1/4	1	NM_001128423.2	ENSP00000379669	P1	Q2QL34-1
MPV17L	ENST00000287594.7 linkuse as main transcript	c.271G>T	p.Val91Leu	missense_variant	1/3	1		ENSP00000287594		Q2QL34-2
MPV17L	ENST00000564148.1 linkuse as main transcript	c.85G>T	p.Val29Leu	missense_variant, NMD_transcript_variant	1/5	4		ENSP00000457012

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000133

AC:

AN:

150060

Hom.:

AF XY:

0.0000125

AC XY:

AN XY:

80270

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000403

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000193

AC:

AN:

1398174

Hom.:

Cov.:

AF XY:

0.0000232

AC XY:

AN XY:

689972

show subpopulations

Gnomad4 AFR exome

AF:

0.000599

Gnomad4 AMR exome

AF:

0.0000279

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:

0.0000517

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.00000946

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 10, 2024

The c.271G>T (p.V91L) alteration is located in exon 1 (coding exon 1) of the MPV17L gene. This alteration results from a G to T substitution at nucleotide position 271, causing the valine (V) at amino acid position 91 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

0.14

BayesDel_addAF

Benign

-0.024

BayesDel_noAF

Benign

-0.27

CADD

Benign

5.0

DANN

Benign

0.56

DEOGEN2

Benign

0.0045

.;T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.64

T;T;T

M_CAP

Uncertain

0.28

MetaRNN

Benign

0.045

T;T;T

MetaSVM

Benign

-0.47

MutationAssessor

Benign

-0.47

N;N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.27

N;N;N

REVEL

Uncertain

0.32

Sift

Benign

0.56

T;T;T

Sift4G

Benign

0.91

T;T;T

Polyphen

0.0010

B;B;.

Vest4

0.068

MutPred

0.36

Gain of helix (P = 0.132);Gain of helix (P = 0.132);Gain of helix (P = 0.132);

MVP

0.22

MPC

0.052

ClinPred

0.0085

GERP RS

-2.9

Varity_R

0.044

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over