19-18193289-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032683.3(MPV17L2):​c.8G>C​(p.Arg3Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000195 in 1,540,488 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

MPV17L2
NM_032683.3 missense

Scores

2
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.142
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]

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=0.026668787).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MPV17L2NM_032683.3 linkc.8G>C p.Arg3Pro missense_variant Exon 1 of 5 ENST00000599612.3 NP_116072.2 Q567V2-1A0A024R7K6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MPV17L2ENST00000599612.3 linkc.8G>C p.Arg3Pro missense_variant Exon 1 of 5 1 NM_032683.3 ENSP00000469836.2 Q567V2-1
MPV17L2ENST00000532896.5 linkn.58G>C non_coding_transcript_exon_variant Exon 1 of 3 2
MPV17L2ENST00000533807.3 linkn.40G>C non_coding_transcript_exon_variant Exon 1 of 4 2
MPV17L2ENST00000534421.1 linkn.72G>C non_coding_transcript_exon_variant Exon 1 of 2 2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152218
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.00000683
AC:
1
AN:
146354
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
82852
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000464
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000144
AC:
2
AN:
1388270
Hom.:
0
Cov.:
31
AF XY:
0.00000145
AC XY:
1
AN XY:
687538
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000128
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.23e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152218
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.00
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
ExAC
AF:
0.00000871
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 12, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.8G>C (p.R3P) alteration is located in exon 1 (coding exon 1) of the MPV17L2 gene. This alteration results from a G to C substitution at nucleotide position 8, causing the arginine (R) at amino acid position 3 to be replaced by a proline (P). 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
0.058
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
8.1
DANN
Benign
0.55
DEOGEN2
Benign
0.00082
T
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.017
N
LIST_S2
Benign
0.38
T
M_CAP
Uncertain
0.21
D
MetaRNN
Benign
0.027
T
MetaSVM
Benign
-0.78
T
MutationAssessor
Benign
-2.5
N
PrimateAI
Uncertain
0.56
T
Sift4G
Benign
0.31
T
Polyphen
0.0
B
Vest4
0.076
MutPred
0.35
Loss of methylation at R3 (P = 0.0077);
MVP
0.17
MPC
0.75
ClinPred
0.048
T
GERP RS
-5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.11
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.

Other links and lift over

dbSNP: rs780288310; hg19: chr19-18304099; API