rs874628

chr19-18193890-A-Gchr19-18193890-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.20

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
MPV17L2	NM_032683.3	c.214A>G	p.Met72Val	missense_variant	2/5	ENST00000599612.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPV17L2	ENST00000599612.3	c.214A>G	p.Met72Val	missense_variant	2/5	1	NM_032683.3	P1
MPV17L2	ENST00000532896.5	n.659A>G		non_coding_transcript_exon_variant	1/3	2
MPV17L2	ENST00000533807.3	n.641A>G		non_coding_transcript_exon_variant	1/4	2
MPV17L2	ENST00000534421.1	n.278A>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36844 AN: 151948 Hom.: 4585 Cov.: 32

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

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.: 36 AF XY: 0.269 AC XY: 195965 AN XY: 727222

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.: 32 AF XY: 0.240 AC XY: 17831 AN XY: 74346

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	T
BayesDel_noAF	Benign	-0.21
Cadd	Benign	22
Dann	Uncertain	0.98
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.080
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	0.062	P;P
PrimateAI	Uncertain	0.53	T
Sift4G	Benign	0.34	T
Polyphen		0.14	B
Vest4		0.26
MPC		1.1
ClinPred		0.029	T
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

Other links and lift over

dbSNP: rs874628; hg19: chr19-18304700; COSMIC: COSV55852679; COSMIC: COSV55852679;