Genetic Variant NM_001128423.2:c.56C>A (chr16-15395953-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001128423.2(MPV17L):c.56C>A(p.Thr19Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000333 in 1,500,220 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

MPV17L
NM_001128423.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.20

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:

ENSG00000261130 (HGNC:):

ENSG00000261130 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPV17L	NM_001128423.2 link	c.56C>A	p.Thr19Asn	missense_variant	Exon 1 of 4	ENST00000396385.4	NP_001121895.1	Q2QL34-1
MPV17L-BMERB1	NM_001414674.1 link	c.56C>A	p.Thr19Asn	missense_variant	Exon 1 of 6		NP_001401603.1
MPV17L	NM_173803.4 link	c.56C>A	p.Thr19Asn	missense_variant	Exon 1 of 3		NP_776164.2	Q2QL34-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPV17L	ENST00000396385.4 link	c.56C>A	p.Thr19Asn	missense_variant	Exon 1 of 4	1	NM_001128423.2	ENSP00000379669.3		Q2QL34-1
ENSG00000261130	ENST00000568766.1 link	c.56C>A	p.Thr19Asn	missense_variant	Exon 1 of 2	2		ENSP00000454340.1		H3BMD7

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

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

GnomAD4 exome

AF:

7.42e-7

AC:

AN:

1348008

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

664834

show subpopulations

Gnomad4 AFR exome

AF:

0.0000365

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0000965

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

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 20, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.56C>A (p.T19N) alteration is located in exon 1 (coding exon 1) of the MPV17L gene. This alteration results from a C to A substitution at nucleotide position 56, causing the threonine (T) at amino acid position 19 to be replaced by an asparagine (N). 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

0.53

BayesDel_addAF

Uncertain

0.066

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.18

.;T;.

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.77

T;D;T

M_CAP

Pathogenic

0.81

MetaRNN

Uncertain

0.47

T;T;T

MetaSVM

Uncertain

0.33

MutationAssessor

Pathogenic

3.0

M;M;.

PrimateAI

Pathogenic

0.94

PROVEAN

Uncertain

-3.0

D;N;D

REVEL

Uncertain

0.35

Sift

Uncertain

0.0060

D;D;D

Sift4G

Uncertain

0.041

D;D;T

Polyphen

0.94

P;P;.

Vest4

0.38

MutPred

0.42

Gain of relative solvent accessibility (P = 0.0289);Gain of relative solvent accessibility (P = 0.0289);Gain of relative solvent accessibility (P = 0.0289);

MVP

0.47

MPC

2.3

ClinPred

0.96

GERP RS

1.6

Varity_R

0.18

gMVP

0.86

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