NM_018116.4:c.113C>G

Variant names:

• chr1-155610453-C-G
• rs1006121390
• NM_018116.4:c.113C>G

Variant summary

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

The NM_018116.4(MSTO1):​c.113C>G​(p.Ser38Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000022 (0 hom., cov: 19)
  • Exomes 𝑓: 0.000011 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MSTO1 NM_018116.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.414
• 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=0.104735166).

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.113C>G	p.Ser38Cys	missense	Exon 2 of 14	NP_060586.2
	MSTO1	NM_001350776.1		c.-175C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 14	NP_001337705.1
	MSTO1	NM_001350777.1		c.-444C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 14	NP_001337706.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSTO1	ENST00000245564.8	TSL:1 MANE Select	c.113C>G	p.Ser38Cys	missense	Exon 2 of 14	ENSP00000245564.3	Q9BUK6-1
	MSTO1	ENST00000368341.8	TSL:2	c.113C>G	p.Ser38Cys	missense	Exon 2 of 13	ENSP00000357325.4	Q9BUK6-7
	MSTO1	ENST00000490743.5	TSL:1	n.113C>G		non_coding_transcript_exon	Exon 2 of 13	ENSP00000476353.1	Q9BUK6-4

Frequencies

GnomAD3 genomes AF: 0.0000224 AC: 3 AN: 134080 Hom.: 0 Cov.: 19

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: 0.0000479

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000121 AC: 1 AN: 82920 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: 0.0000334

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000115 AC: 8 AN: 698300 Hom.: 0 Cov.: 9 AF XY: 0.0000194 AC XY: 7 AN XY: 361110

African (AFR) AF: 0.00 AC: 0 AN: 18400

American (AMR) AF: 0.0000310 AC: 1 AN: 32290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17920

East Asian (EAS) AF: 0.00 AC: 0 AN: 32686

South Asian (SAS) AF: 0.00 AC: 0 AN: 59328

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2576

European-Non Finnish (NFE) AF: 0.0000149 AC: 7 AN: 468238

Other (OTH) AF: 0.00 AC: 0 AN: 34980

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000224 AC: 3 AN: 134080 Hom.: 0 Cov.: 19 AF XY: 0.0000156 AC XY: 1 AN XY: 64154

African (AFR) AF: 0.00 AC: 0 AN: 34718

American (AMR) AF: 0.00 AC: 0 AN: 13546

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3290

East Asian (EAS) AF: 0.00 AC: 0 AN: 4502

South Asian (SAS) AF: 0.00 AC: 0 AN: 3514

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9014

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.0000479 AC: 3 AN: 62628

Other (OTH) AF: 0.00 AC: 0 AN: 1748

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

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	0.073
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	15
DANN	Benign	0.84
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.41
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.11
Sift	Uncertain	0.025	D
Sift4G	Uncertain	0.053	T
Polyphen		0.58	P
Vest4		0.10
MutPred		0.41		Loss of disorder (P = 0.0125)
MVP		0.42
MPC		2.3
ClinPred		0.10	T
GERP RS		-1.8
PromoterAI		0.012	Neutral
Varity_R		0.077
gMVP		0.29
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1006121390; hg19: chr1-155580244;