1-155610270-G-A

Variant summary

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

The NM_018116.4(MSTO1):c.22G>A(p.Val8Met) variant causes a missense change. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00022 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MSTO1 NM_018116.4 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: 4.08

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSTO1	NM_018116.4	c.22G>A	p.Val8Met	missense_variant	1/14	ENST00000245564.8
LOC105371452	XR_922171.2	n.77-378C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSTO1	ENST00000245564.8	c.22G>A	p.Val8Met	missense_variant	1/14	1	NM_018116.4	P1
	ENST00000456382.2	n.103+8C>T		splice_region_variant, intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 7 AN: 150766 Hom.: 0 Cov.: 27 FAILED QC

Gnomad AFR AF: 0.0000488

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000660

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000190

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000296

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000202 AC: 25 AN: 123620 Hom.: 0 AF XY: 0.000257 AC XY: 17 AN XY: 66222

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000582

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000531

Gnomad SAS exome AF: 0.000251

Gnomad FIN exome AF: 0.000426

Gnomad NFE exome AF: 0.000182

Gnomad OTH exome AF: 0.000326

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000219 AC: 152 AN: 695628 Hom.: 0 Cov.: 9 AF XY: 0.000247 AC XY: 88 AN XY: 356964

Gnomad4 AFR exome AF: 0.000116

Gnomad4 AMR exome AF: 0.0000804

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000316

Gnomad4 SAS exome AF: 0.000398

Gnomad4 FIN exome AF: 0.000229

Gnomad4 NFE exome AF: 0.000218

Gnomad4 OTH exome AF: 0.0000877

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000464 AC: 7 AN: 150880 Hom.: 0 Cov.: 27 AF XY: 0.0000679 AC XY: 5 AN XY: 73688

Gnomad4 AFR AF: 0.0000487

Gnomad4 AMR AF: 0.0000659

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000190

Gnomad4 NFE AF: 0.0000296

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00122 Hom.: 0

ExAC AF: 0.0000636 AC: 7

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome Uncertain:2

Uncertain significance, no assertion criteria provided	literature only	OMIM	Aug 28, 2023	- -
Uncertain significance, criteria provided, single submitter	clinical testing	3billion	Jan 03, 2022	Same nucleotide change resulting in same amino acid change has been previously reported to be associated with MSTO1 related disorder (ClinVar ID: VCV000438835, PS1_P). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000175, PM2_M). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.644, PP3_P). Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline. -

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2023

Reported in the heterozygous state in a family with mitochondrial myopathy, ataxia, minor dysmorphisms, endocrine dysfunctions, and psychiatric symptoms (Gal et al., 2017); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 34426522, 33672784, 30684668, 29339779, 31604776, 36468072, 33222031, 28554942) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
Cadd	Pathogenic	26
Dann	Uncertain	1.0
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.052	D
MetaRNN	Uncertain	0.59	D;D;D
MetaSVM	Uncertain	-0.20	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.89	D
Polyphen		1.0	.;D;.
Vest4		0.73, 0.70
MutPred		0.72		Gain of disorder (P = 0.0831);Gain of disorder (P = 0.0831);Gain of disorder (P = 0.0831);
MVP		0.78
MPC		3.3
ClinPred		0.20	T
GERP RS		3.3
Varity_R		0.18
gMVP		0.62

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: rs762798018; hg19: chr1-155580061; COSMIC: COSV55471170; COSMIC: COSV55471170;