Variant 19-18193352-C-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_032683.3(MPV17L2):c.71C>T(p.Ala24Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000454 in 1,564,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

MPV17L2
NM_032683.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.938

Variant links:

Genes affected

MPV17L2 (HGNC:28177): (MPV17 mitochondrial inner membrane protein like 2) Involved in mitochondrial ribosome assembly and positive regulation of mitochondrial translation. Located in mitochondrial inner membrane. Part of mitochondrial large ribosomal subunit. [provided by Alliance of Genome Resources, Apr 2022]

MPV17L2 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=0.016910583).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPV17L2	NM_032683.3 linkuse as main transcript	c.71C>T	p.Ala24Val	missense_variant	1/5	ENST00000599612.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPV17L2	ENST00000599612.3 linkuse as main transcript	c.71C>T	p.Ala24Val	missense_variant	1/5	1	NM_032683.3	P1	Q567V2-1
MPV17L2	ENST00000532896.5 linkuse as main transcript	n.121C>T		non_coding_transcript_exon_variant	1/3	2
MPV17L2	ENST00000533807.3 linkuse as main transcript	n.103C>T		non_coding_transcript_exon_variant	1/4	2
MPV17L2	ENST00000534421.1 linkuse as main transcript	n.135C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000664

AC:

AN:

165778

Hom.:

AF XY:

0.0000974

AC XY:

AN XY:

92424

show subpopulations

Gnomad AFR exome

AF:

0.00114

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000821

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000144

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000262

AC:

AN:

1412594

Hom.:

Cov.:

AF XY:

0.0000257

AC XY:

AN XY:

700368

show subpopulations

Gnomad4 AFR exome

AF:

0.000809

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000617

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000183

Gnomad4 OTH exome

AF:

0.0000855

GnomAD4 genome

AF:

0.000223

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.000796

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000253

ESP6500AA

AF:

0.00111

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000343

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

May 28, 2023

The c.71C>T (p.A24V) alteration is located in exon 1 (coding exon 1) of the MPV17L2 gene. This alteration results from a C to T substitution at nucleotide position 71, causing the alanine (A) at amino acid position 24 to be replaced by a valine (V). 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

0.11

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.25

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.0072

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.80

M_CAP

Pathogenic

0.33

MetaRNN

Benign

0.017

MetaSVM

Benign

-0.69

MutationAssessor

Benign

0.83

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.74

Sift4G

Benign

0.48

Polyphen

0.0070

Vest4

0.19

MVP

0.34

MPC

0.52

ClinPred

0.043

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.052

gMVP

0.51

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