19-18195039-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_032683.3(MPV17L2):​c.517G>C​(p.Gly173Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

MPV17L2
NM_032683.3 missense

Scores

2
5
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.15
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 Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.833

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MPV17L2NM_032683.3 linkc.517G>C p.Gly173Arg missense_variant Exon 4 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.517G>C p.Gly173Arg missense_variant Exon 4 of 5 1 NM_032683.3 ENSP00000469836.2 Q567V2-1
MPV17L2ENST00000532896.5 linkn.885G>C non_coding_transcript_exon_variant Exon 2 of 3 2
MPV17L2ENST00000533807.3 linkn.944G>C non_coding_transcript_exon_variant Exon 3 of 4 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000401
AC:
1
AN:
249436
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135338
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000884
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000752
AC:
11
AN:
1461856
Hom.:
0
Cov.:
34
AF XY:
0.00000963
AC XY:
7
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 24, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.517G>C (p.G173R) alteration is located in exon 4 (coding exon 4) of the MPV17L2 gene. This alteration results from a G to C substitution at nucleotide position 517, causing the glycine (G) at amino acid position 173 to be replaced by an arginine (R). 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
Pathogenic
0.96
BayesDel_addAF
Uncertain
0.092
D
BayesDel_noAF
Benign
-0.11
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.34
T
Eigen
Benign
0.092
Eigen_PC
Benign
-0.010
FATHMM_MKL
Benign
0.45
N
LIST_S2
Uncertain
0.91
D
M_CAP
Uncertain
0.17
D
MetaRNN
Pathogenic
0.83
D
MetaSVM
Benign
-0.35
T
MutationAssessor
Benign
1.9
L
PrimateAI
Uncertain
0.50
T
Sift4G
Benign
0.35
T
Polyphen
0.93
P
Vest4
0.57
MutPred
0.74
Gain of catalytic residue at G173 (P = 0.0715);
MVP
0.54
MPC
1.4
ClinPred
0.76
D
GERP RS
0.70
Varity_R
0.057
gMVP
0.63

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: rs772772653; hg19: chr19-18305849; API