1-155610468-G-C

Variant names:

• chr1-155610468-G-C
• rs1191380112
• NM_018116.4:c.128G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_018116.4(MSTO1):​c.128G>C​(p.Gly43Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 18)
  • Exomes 𝑓: 0.000019 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MSTO1 NM_018116.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0440
• 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

LOC105371452 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15296996).

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.128G>C	p.Gly43Ala	missense	Exon 2 of 14	NP_060586.2
	MSTO1	NM_001256532.1		c.128G>C	p.Gly43Ala	missense	Exon 2 of 14	NP_001243461.1	Q9BUK6-2
	MSTO1	NM_001350772.1		c.128G>C	p.Gly43Ala	missense	Exon 2 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.128G>C	p.Gly43Ala	missense	Exon 2 of 14	ENSP00000245564.3	Q9BUK6-1
	MSTO1	ENST00000368341.8	TSL:2	c.128G>C	p.Gly43Ala	missense	Exon 2 of 13	ENSP00000357325.4	Q9BUK6-7
	MSTO1	ENST00000490743.5	TSL:1	n.128G>C		non_coding_transcript_exon	Exon 2 of 13	ENSP00000476353.1	Q9BUK6-4

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD2 exomes AF: 0.000107 AC: 9 AN: 83840 AF XY: 0.0000921

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000488

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000190 AC: 13 AN: 685840 Hom.: 0 Cov.: 9 AF XY: 0.0000253 AC XY: 9 AN XY: 355978

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 18246

American (AMR) AF: 0.000367 AC: 12 AN: 32664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18120

East Asian (EAS) AF: 0.00 AC: 0 AN: 32816

South Asian (SAS) AF: 0.00 AC: 0 AN: 60116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32194

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2554

European-Non Finnish (NFE) AF: 0.00000220 AC: 1 AN: 454640

Other (OTH) AF: 0.00 AC: 0 AN: 34490

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 18

Alfa AF: 0.0000843 Hom.: 0

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	Benign	0.080
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0041	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.044
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.20
Sift	Benign	0.036	D
Sift4G	Benign	0.089	T
Polyphen		0.93	P
Vest4		0.11
MutPred		0.45		Gain of glycosylation at P41 (P = 0.0984)
MVP		0.69
MPC		2.0
ClinPred		0.066	T
GERP RS		3.2
PromoterAI		-0.00030	Neutral
Varity_R		0.048
gMVP		0.33
Mutation Taster		=90/10	polymorphism

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: rs1191380112; hg19: chr1-155580259;