19-18193890-A-C

Variant names:

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

Variant summary

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

The NM_032683.3(MPV17L2):​c.214A>C​(p.Met72Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. M72V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MPV17L2 NM_032683.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.20
• 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=0.36607057).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPV17L2	NM_032683.3	MANE Select	c.214A>C	p.Met72Leu	missense	Exon 2 of 5	NP_116072.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPV17L2	ENST00000599612.3	TSL:1 MANE Select	c.214A>C	p.Met72Leu	missense	Exon 2 of 5	ENSP00000469836.2
	MPV17L2	ENST00000532896.5	TSL:2	n.659A>C		non_coding_transcript_exon	Exon 1 of 3
	MPV17L2	ENST00000533807.3	TSL:2	n.641A>C		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Benign	0.89
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.095	D
MetaRNN	Benign	0.37	T
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Benign	0.57	N
PhyloP100		3.2
PrimateAI	Uncertain	0.57	T
Sift4G	Benign	0.64	T
Polyphen		0.0020	B
Vest4		0.32
MutPred		0.33		Loss of sheet (P = 0.0817)
MVP		0.21
MPC		0.55
ClinPred		0.69	D
GERP RS		4.5
Varity_R		0.50
gMVP		0.63
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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;