rs1553295536

Variant names:

• chr1-155613078-C-A
• rs1553295536
• NM_018116.4:c.1128C>A

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 4 publications found

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]

MSTO1 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Broad Center for Mendelian Genomics, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 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 VariationId is 438832.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018116.4. 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
	MSTO1	NM_018116.4	MANE Select	c.1128C>A	p.Phe376Leu	missense	Exon 11 of 14	NP_060586.2
	MSTO1	NM_001256532.1		c.1128C>A	p.Phe376Leu	missense	Exon 11 of 14	NP_001243461.1	Q9BUK6-2
	MSTO1	NM_001350772.1		c.1128C>A	p.Phe376Leu	missense	Exon 11 of 14	NP_001337701.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSTO1	ENST00000245564.8	TSL:1 MANE Select	c.1128C>A	p.Phe376Leu	missense	Exon 11 of 14	ENSP00000245564.3	Q9BUK6-1
	MSTO1	ENST00000368341.8	TSL:2	c.1023C>A	p.Phe341Leu	missense	Exon 10 of 13	ENSP00000357325.4	Q9BUK6-7
	MSTO1	ENST00000483734.5	TSL:1	n.1250C>A		non_coding_transcript_exon	Exon 10 of 13

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 30

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.75
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.20
Sift	Benign	0.14	T
Sift4G	Benign	0.18	T
Polyphen		0.22	B
Vest4		0.44
MutPred		0.79		Gain of glycosylation at P377 (P = 0.055)
MVP		0.46
MPC		1.1
ClinPred		0.91	D
GERP RS		2.8
PromoterAI		-0.0070	Neutral
Varity_R		0.29
gMVP		0.73
Mutation Taster		=6/94	disease causing (ClinVar)

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: rs1553295536; hg19: chr1-155582869;