rs1553295536

Positions:

• chr1-155613078-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_018116.4(MSTO1):​c.1128C>A​(p.Phe376Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 30)
• Consequence: MSTO1 NM_018116.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.746

Genes affected

MSTO1 (HGNC:29678): (misato mitochondrial distribution and morphology regulator 1) Involved in mitochondrion distribution. Located in cytosol and mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-155613078-C-A is Pathogenic according to our data. Variant chr1-155613078-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 438832.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-155613078-C-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSTO1	NM_018116.4	c.1128C>A	p.Phe376Leu	missense_variant	11/14	ENST00000245564.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSTO1	ENST00000245564.8	c.1128C>A	p.Phe376Leu	missense_variant	11/14	1	NM_018116.4	P1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 30

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 22, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	.;T;.
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.62	T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.72	D;D;D
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.5	.;M;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.5	.;D;D
REVEL	Benign	0.20
Sift	Benign	0.14	.;T;T
Sift4G	Benign	0.18	.;T;T
Polyphen		0.22, 0.81	.;B;P
Vest4		0.44, 0.42
MutPred		0.79		Gain of glycosylation at P377 (P = 0.055);Gain of glycosylation at P377 (P = 0.055);.;
MVP		0.46
MPC		1.1
ClinPred		0.91	D
GERP RS		2.8
Varity_R		0.29
gMVP		0.73

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

Other links and lift over

dbSNP: rs1553295536; hg19: chr1-155582869;