Variant 16-15400850-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001128423.2(MPV17L):c.374C>G(p.Thr125Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000706 in 1,601,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

MPV17L
NM_001128423.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.46

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16041076).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MPV17L	NM_001128423.2 linkuse as main transcript	c.374C>G	p.Thr125Ser	missense_variant	2/4	ENST00000396385.4	NP_001121895.1
MPV17L-BMERB1	NM_001414674.1 linkuse as main transcript	c.310+4643C>G		intron_variant			NP_001401603.1
MPV17L	NM_173803.4 linkuse as main transcript	c.310+4643C>G		intron_variant			NP_776164.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPV17L	ENST00000396385.4 linkuse as main transcript	c.374C>G	p.Thr125Ser	missense_variant	2/4	1	NM_001128423.2	ENSP00000379669	P1	Q2QL34-1
MPV17L	ENST00000287594.7 linkuse as main transcript	c.310+4643C>G		intron_variant		1		ENSP00000287594		Q2QL34-2
MPV17L	ENST00000564148.1 linkuse as main transcript	c.*147C>G		3_prime_UTR_variant, NMD_transcript_variant	3/5	4		ENSP00000457012

Frequencies

GnomAD3 genomes

AF:

0.000311

AC:

AN:

151092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00112

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:

0.000483

GnomAD3 exomes

AF:

0.0000931

AC:

AN:

247060

Hom.:

AF XY:

0.0000747

AC XY:

AN XY:

133872

show subpopulations

Gnomad AFR exome

AF:

0.00133

Gnomad AMR exome

AF:

0.0000598

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:

0.0000441

AC:

AN:

1450090

Hom.:

Cov.:

AF XY:

0.0000416

AC XY:

AN XY:

721378

show subpopulations

Gnomad4 AFR exome

AF:

0.00147

Gnomad4 AMR exome

AF:

0.0000457

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:

9.05e-7

Gnomad4 OTH exome

AF:

0.000201

GnomAD4 genome

AF:

0.000324

AC:

AN:

151206

Hom.:

Cov.:

AF XY:

0.000325

AC XY:

AN XY:

73842

show subpopulations

Gnomad4 AFR

AF:

0.00117

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:

0.000478

Alfa

AF:

0.000101

Hom.:

Bravo

AF:

0.000476

ESP6500AA

AF:

0.00191

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000140

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

Jan 04, 2024

The c.374C>G (p.T125S) alteration is located in exon 2 (coding exon 2) of the MPV17L gene. This alteration results from a C to G substitution at nucleotide position 374, causing the threonine (T) at amino acid position 125 to be replaced by a serine (S). 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

Uncertain

0.44

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.55

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.60

M_CAP

Benign

0.044

MetaRNN

Benign

0.16

MetaSVM

Uncertain

0.64

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

1.0

D;N

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-2.8

REVEL

Uncertain

0.55

Sift

Benign

0.083

Sift4G

Benign

0.16

Polyphen

0.97

Vest4

0.53

MutPred

0.62

Gain of catalytic residue at T125 (P = 0.0253);

MVP

0.67

MPC

0.31

ClinPred

0.10

GERP RS

5.2

Varity_R

0.24

gMVP

0.50

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

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