chr1-155610277-C-G

Variant names:

• chr1-155610277-C-G
• NM_018116.4:c.29C>G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_018116.4(MSTO1):​c.29C>G​(p.Thr10Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 27)
• Consequence: MSTO1 NM_018116.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.43
• Publications: 0 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

ENSG00000232519 (HGNC:):

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.971

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.29C>G	p.Thr10Arg	missense	Exon 1 of 14	NP_060586.2
	MSTO1	NM_001256532.1		c.29C>G	p.Thr10Arg	missense	Exon 1 of 14	NP_001243461.1	Q9BUK6-2
	MSTO1	NM_001350772.1		c.29C>G	p.Thr10Arg	missense	Exon 1 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.29C>G	p.Thr10Arg	missense	Exon 1 of 14	ENSP00000245564.3	Q9BUK6-1
	MSTO1	ENST00000368341.8	TSL:2	c.29C>G	p.Thr10Arg	missense	Exon 1 of 13	ENSP00000357325.4	Q9BUK6-7
	MSTO1	ENST00000490743.5	TSL:1	n.29C>G		non_coding_transcript_exon	Exon 1 of 13	ENSP00000476353.1	Q9BUK6-4

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Cov.: 11

GnomAD4 genome Cov.: 27

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.30
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.073	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Uncertain	0.18	D
MutationAssessor	Pathogenic	3.3	M
PhyloP100		5.4
PrimateAI	Pathogenic	0.92	D
PROVEAN	Pathogenic	-5.0	D
REVEL	Pathogenic	0.73
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.94
MutPred		0.87		Gain of MoRF binding (P = 0.0056)
MVP		0.90
MPC		3.6
ClinPred		1.0	D
GERP RS		3.3
PromoterAI		0.050	Neutral
Varity_R		0.88
gMVP		0.91
Mutation Taster		=47/53	disease causing

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

hg19: chr1-155580068;