rs1269806399

Variant names:

• chr16-15395986-C-T
• rs1269806399
• NM_001128423.2:c.89C>T

Variant summary

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

The NM_001128423.2(MPV17L):​c.89C>T​(p.Ala30Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000542 in 1,513,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000057 (0 hom.)
• Consequence: MPV17L NM_001128423.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.901
• Publications: 0 publications found

Genes affected

MPV17L (HGNC:26827): (MPV17 mitochondrial inner membrane protein like) Involved in negative regulation of hydrogen peroxide biosynthetic process; negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway; and reactive oxygen species metabolic process. Located in peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000261130 (HGNC:):

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=0.39747816).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128423.2. 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
	MPV17L	NM_001128423.2	MANE Select	c.89C>T	p.Ala30Val	missense	Exon 1 of 4	NP_001121895.1	Q2QL34-1
	MPV17L-BMERB1	NM_001414674.1		c.89C>T	p.Ala30Val	missense	Exon 1 of 6	NP_001401603.1
	MPV17L	NM_173803.4		c.89C>T	p.Ala30Val	missense	Exon 1 of 3	NP_776164.2	Q2QL34-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPV17L	ENST00000396385.4	TSL:1 MANE Select	c.89C>T	p.Ala30Val	missense	Exon 1 of 4	ENSP00000379669.3	Q2QL34-1
	MPV17L	ENST00000287594.7	TSL:1	c.89C>T	p.Ala30Val	missense	Exon 1 of 3	ENSP00000287594.6	Q2QL34-2
	ENSG00000261130	ENST00000568766.1	TSL:2	c.89C>T	p.Ala30Val	missense	Exon 1 of 2	ENSP00000454340.1	H3BMD7

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000482

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000186 AC: 2 AN: 107814 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000494

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000573 AC: 78 AN: 1361326 Hom.: 0 Cov.: 31 AF XY: 0.0000566 AC XY: 38 AN XY: 670894

African (AFR) AF: 0.00 AC: 0 AN: 28478

American (AMR) AF: 0.00 AC: 0 AN: 33816

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23820

East Asian (EAS) AF: 0.00 AC: 0 AN: 33282

South Asian (SAS) AF: 0.00 AC: 0 AN: 75632

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35240

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3998

European-Non Finnish (NFE) AF: 0.0000719 AC: 77 AN: 1070254

Other (OTH) AF: 0.0000176 AC: 1 AN: 56806

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152210 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74354

African (AFR) AF: 0.0000482 AC: 2 AN: 41468

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000511 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.79	T
M_CAP	Pathogenic	0.64	D
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.34	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.90
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.30
Sift	Benign	0.29	T
Sift4G	Uncertain	0.019	D
Polyphen		0.94	P
Vest4		0.16
MutPred		0.38		Loss of disorder (P = 0.0893)
MVP		0.24
MPC		2.3
ClinPred		0.63	D
GERP RS		2.7
PromoterAI		-0.088	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.11
gMVP		0.64
Mutation Taster		=90/10	polymorphism

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: rs1269806399; hg19: chr16-15489843;