rs141537147

Variant names:

• chr1-155610262-C-G
• rs141537147
• NM_018116.4:c.14C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-155610262-C-G
• chr1-155610262-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018116.4(MSTO1):​c.14C>G​(p.Ala5Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000785 in 764,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A5V) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: MSTO1 NM_018116.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60
• Publications: 3 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24076483).

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.14C>G	p.Ala5Gly	missense	Exon 1 of 14	NP_060586.2
	MSTO1	NM_001256532.1		c.14C>G	p.Ala5Gly	missense	Exon 1 of 14	NP_001243461.1	Q9BUK6-2
	MSTO1	NM_001350772.1		c.14C>G	p.Ala5Gly	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.14C>G	p.Ala5Gly	missense	Exon 1 of 14	ENSP00000245564.3	Q9BUK6-1
	MSTO1	ENST00000368341.8	TSL:2	c.14C>G	p.Ala5Gly	missense	Exon 1 of 13	ENSP00000357325.4	Q9BUK6-7
	MSTO1	ENST00000490743.5	TSL:1	n.14C>G		non_coding_transcript_exon	Exon 1 of 13	ENSP00000476353.1	Q9BUK6-4

Frequencies

GnomAD3 genomes AF: 0.00000662 AC: 1 AN: 151170 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000873 AC: 1 AN: 114550 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000181

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000816 AC: 5 AN: 613004 Hom.: 0 Cov.: 8 AF XY: 0.0000126 AC XY: 4 AN XY: 317664

African (AFR) AF: 0.00 AC: 0 AN: 15854

American (AMR) AF: 0.00 AC: 0 AN: 23762

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14852

East Asian (EAS) AF: 0.00 AC: 0 AN: 34108

South Asian (SAS) AF: 0.00 AC: 0 AN: 53202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34524

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2248

European-Non Finnish (NFE) AF: 0.00000993 AC: 4 AN: 402986

Other (OTH) AF: 0.0000318 AC: 1 AN: 31468

GnomAD4 genome AF: 0.00000662 AC: 1 AN: 151170 Hom.: 0 Cov.: 28 AF XY: 0.0000136 AC XY: 1 AN XY: 73754

African (AFR) AF: 0.00 AC: 0 AN: 41106

American (AMR) AF: 0.00 AC: 0 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3452

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10492

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67758

Other (OTH) AF: 0.00 AC: 0 AN: 2066

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0093	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.6
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.039
Sift	Benign	0.067	T
Sift4G	Benign	0.18	T
Polyphen		0.86	P
Vest4		0.21
MutPred		0.23		Gain of disorder (P = 0.0794)
MVP		0.41
MPC		2.3
ClinPred		0.23	T
GERP RS		3.3
PromoterAI		0.18	Neutral
Varity_R		0.089
gMVP		0.31
Mutation Taster		=88/12	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: rs141537147; hg19: chr1-155580053;