19-18193460-G-T

Variant names:

• chr19-18193460-G-T
• rs552171425
• NM_032683.3:c.179G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032683.3(MPV17L2):​c.179G>T​(p.Arg60Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000726 in 1,376,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R60Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: MPV17L2 NM_032683.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.64
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2778212).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032683.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPV17L2	NM_032683.3	MANE Select	c.179G>T	p.Arg60Leu	missense	Exon 1 of 5	NP_116072.2	Q567V2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPV17L2	ENST00000599612.3	TSL:1 MANE Select	c.179G>T	p.Arg60Leu	missense	Exon 1 of 5	ENSP00000469836.2	Q567V2-1
	MPV17L2	ENST00000865126.1		c.179G>T	p.Arg60Leu	missense	Exon 1 of 4	ENSP00000535185.1
	MPV17L2	ENST00000532896.5	TSL:2	n.229G>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.26e-7 AC: 1 AN: 1376626 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 680962

African (AFR) AF: 0.00 AC: 0 AN: 29420

American (AMR) AF: 0.00 AC: 0 AN: 33780

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22378

East Asian (EAS) AF: 0.00 AC: 0 AN: 36342

South Asian (SAS) AF: 0.00 AC: 0 AN: 75868

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36060

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4956

European-Non Finnish (NFE) AF: 9.25e-7 AC: 1 AN: 1080892

Other (OTH) AF: 0.00 AC: 0 AN: 56930

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.29
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.74	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.43	T
MutationAssessor	Benign	0.95	L
PhyloP100		1.6
PrimateAI	Uncertain	0.58	T
Sift4G	Benign	0.32	T
Polyphen		0.0010	B
Vest4		0.34
MutPred		0.48		Loss of disorder (P = 0.0267)
MVP		0.39
MPC		0.65
ClinPred		0.18	T
GERP RS		4.0
PromoterAI		0.045	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.20
gMVP		0.56
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs552171425; hg19: chr19-18304270;