Variant chr19-18193890-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032683.3(MPV17L2):c.214A>G(p.Met72Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 1,613,910 control chromosomes in the GnomAD database, including 59,626 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.24 ( 4586 hom., cov: 32)

Exomes 𝑓: 0.27 ( 55040 hom. )

Consequence

MPV17L2
NM_032683.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.20

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:

MPV17L2 (HGNC:):

MPV17L2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002426654).

BP6

Variant 19-18193890-A-G is Benign according to our data. Variant chr19-18193890-A-G is described in ClinVar as [Benign]. Clinvar id is 1258481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPV17L2	NM_032683.3 linkuse as main transcript	c.214A>G	p.Met72Val	missense_variant	2/5	ENST00000599612.3	NP_116072.2	Q567V2-1A0A024R7K6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MPV17L2	ENST00000599612.3 linkuse as main transcript	c.214A>G	p.Met72Val	missense_variant	2/5	1	NM_032683.3	ENSP00000469836.2	Q567V2-1
MPV17L2	ENST00000532896.5 linkuse as main transcript	n.659A>G		non_coding_transcript_exon_variant	1/3	2
MPV17L2	ENST00000533807.3 linkuse as main transcript	n.641A>G		non_coding_transcript_exon_variant	1/4	2
MPV17L2	ENST00000534421.1 linkuse as main transcript	n.278A>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.242

AC:

36844

AN:

151948

Hom.:

4585

Cov.:

show subpopulations

Gnomad AFR

AF:

0.201

Gnomad AMI

AF:

0.194

Gnomad AMR

AF:

0.214

Gnomad ASJ

AF:

0.336

Gnomad EAS

AF:

0.0712

Gnomad SAS

AF:

0.175

Gnomad FIN

AF:

0.264

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.283

Gnomad OTH

AF:

0.274

GnomAD3 exomes

AF:

0.237

AC:

59033

AN:

249464

Hom.:

7625

AF XY:

0.242

AC XY:

32746

AN XY:

135332

show subpopulations

Gnomad AFR exome

AF:

0.201

Gnomad AMR exome

AF:

0.177

Gnomad ASJ exome

AF:

0.356

Gnomad EAS exome

AF:

0.0776

Gnomad SAS exome

AF:

0.194

Gnomad FIN exome

AF:

0.263

Gnomad NFE exome

AF:

0.279

Gnomad OTH exome

AF:

0.268

GnomAD4 exome

AF:

0.270

AC:

394680

AN:

1461844

Hom.:

55040

Cov.:

AF XY:

0.269

AC XY:

195965

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.202

Gnomad4 AMR exome

AF:

0.181

Gnomad4 ASJ exome

AF:

0.348

Gnomad4 EAS exome

AF:

0.0798

Gnomad4 SAS exome

AF:

0.196

Gnomad4 FIN exome

AF:

0.259

Gnomad4 NFE exome

AF:

0.287

Gnomad4 OTH exome

AF:

0.266

GnomAD4 genome

AF:

0.242

AC:

36856

AN:

152066

Hom.:

4586

Cov.:

AF XY:

0.240

AC XY:

17831

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.201

Gnomad4 AMR

AF:

0.214

Gnomad4 ASJ

AF:

0.336

Gnomad4 EAS

AF:

0.0714

Gnomad4 SAS

AF:

0.176

Gnomad4 FIN

AF:

0.264

Gnomad4 NFE

AF:

0.283

Gnomad4 OTH

AF:

0.270

Alfa

AF:

0.279

Hom.:

15016

Bravo

AF:

0.241

TwinsUK

AF:

0.282

AC:

1046

ALSPAC

AF:

0.295

AC:

1136

ESP6500AA

AF:

0.190

AC:

778

ESP6500EA

AF:

0.276

AC:

2318

ExAC

AF:

0.234

AC:

28328

Asia WGS

AF:

0.116

AC:

409

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 10, 2019	This variant is associated with the following publications: (PMID: 21833088, 29083408) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.011

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.080

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.90

MetaRNN

Benign

0.0024

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.1

PrimateAI

Uncertain

0.53

Sift4G

Benign

0.34

Polyphen

0.14

Vest4

0.26

MPC

1.1

ClinPred

0.029

GERP RS

4.5

Varity_R

0.46

gMVP

0.68

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