chr1-155610327-C-T

Variant names:

• chr1-155610327-C-T
• rs1673545403
• NM_018116.4:c.79C>T

Variant summary

Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_018116.4(MSTO1):​c.79C>T​(p.Gln27*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000471 in 849,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 0.0000047 (0 hom.)
• Consequence: MSTO1 NM_018116.4 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.05
• Publications: 1 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 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 16 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-155610327-C-T is Pathogenic according to our data. Variant chr1-155610327-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 987950.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.79C>T	p.Gln27*	stop_gained	Exon 1 of 14	NP_060586.2
	MSTO1	NM_001256532.1		c.79C>T	p.Gln27*	stop_gained	Exon 1 of 14	NP_001243461.1	Q9BUK6-2
	MSTO1	NM_001350772.1		c.79C>T	p.Gln27*	stop_gained	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.79C>T	p.Gln27*	stop_gained	Exon 1 of 14	ENSP00000245564.3	Q9BUK6-1
	MSTO1	ENST00000368341.8	TSL:2	c.79C>T	p.Gln27*	stop_gained	Exon 1 of 13	ENSP00000357325.4	Q9BUK6-7
	MSTO1	ENST00000490743.5	TSL:1	n.79C>T		non_coding_transcript_exon	Exon 1 of 13	ENSP00000476353.1	Q9BUK6-4

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome AF: 0.00000471 AC: 4 AN: 849286 Hom.: 0 Cov.: 11 AF XY: 0.00000935 AC XY: 4 AN XY: 427730

African (AFR) AF: 0.00 AC: 0 AN: 20074

American (AMR) AF: 0.00 AC: 0 AN: 24244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16312

East Asian (EAS) AF: 0.0000868 AC: 3 AN: 34564

South Asian (SAS) AF: 0.0000173 AC: 1 AN: 57848

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 620788

Other (OTH) AF: 0.00 AC: 0 AN: 39108

GnomAD4 genome Cov.: 26

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
BayesDel_addAF	Pathogenic	0.54	D
BayesDel_noAF	Pathogenic	0.54
CADD	Pathogenic	45
DANN	Uncertain	1.0
Eigen	Pathogenic	0.75
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Benign	0.64	D
PhyloP100		3.0
Vest4		0.067
GERP RS		3.2
PromoterAI		0.021	Neutral
Mutation Taster		=2/198	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: rs1673545403; hg19: chr1-155580118;