19-18193890-A-G

Variant names:

• chr19-18193890-A-G
• rs874628
• NM_032683.3:c.214A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.20
• Publications: 108 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
MPV17L2	NM_032683.3	c.214A>G	p.Met72Val	missense_variant	Exon 2 of 5	ENST00000599612.3	NP_116072.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPV17L2	ENST00000599612.3	c.214A>G	p.Met72Val	missense_variant	Exon 2 of 5	1	NM_032683.3	ENSP00000469836.2
MPV17L2	ENST00000532896.5	n.659A>G		non_coding_transcript_exon_variant	Exon 1 of 3	2
MPV17L2	ENST00000533807.3	n.641A>G		non_coding_transcript_exon_variant	Exon 1 of 4	2
MPV17L2	ENST00000534421.1	n.278A>G		non_coding_transcript_exon_variant	Exon 2 of 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

GnomAD2 exomes AF: 0.237 AC: 59033 AN: 249464 AF XY: 0.242

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 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

African (AFR) AF: 0.202 AC: 6756 AN: 33480

American (AMR) AF: 0.181 AC: 8105 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 9082 AN: 26130

East Asian (EAS) AF: 0.0798 AC: 3170 AN: 39700

South Asian (SAS) AF: 0.196 AC: 16918 AN: 86258

European-Finnish (FIN) AF: 0.259 AC: 13848 AN: 53414

Middle Eastern (MID) AF: 0.347 AC: 2002 AN: 5766

European-Non Finnish (NFE) AF: 0.287 AC: 318736 AN: 1111980

Other (OTH) AF: 0.266 AC: 16063 AN: 60392

GnomAD4 genome AF: 0.242 AC: 36856 AN: 152066 Hom.: 4586 Cov.: 32 AF XY: 0.240 AC XY: 17831 AN XY: 74346

African (AFR) AF: 0.201 AC: 8317 AN: 41462

American (AMR) AF: 0.214 AC: 3265 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 1168 AN: 3472

East Asian (EAS) AF: 0.0714 AC: 369 AN: 5170

South Asian (SAS) AF: 0.176 AC: 849 AN: 4818

European-Finnish (FIN) AF: 0.264 AC: 2795 AN: 10580

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19250 AN: 67978

Other (OTH) AF: 0.270 AC: 569 AN: 2104

Alfa AF: 0.270 Hom.: 27338

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

Submissions by phenotype

not provided Benign:2

Jan 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 21833088, 29083408)

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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
PhyloP100		3.2
PrimateAI	Uncertain	0.53	T
Sift4G	Benign	0.34	T
Vest4		0.26
ClinPred		0.029	T
GERP RS		4.5
Varity_R		0.46
gMVP		0.68
Mutation Taster		=92/8	polymorphism (auto)

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

Other links and lift over

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