chr1-155610444-C-T

Variant names:

• chr1-155610444-C-T
• rs762447527
• NM_018116.4:c.104C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018116.4(MSTO1):​c.104C>T​(p.Ala35Val) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A35G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000073 (0 hom., cov: 20)
  • Exomes 𝑓: 0.0000056 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MSTO1 NM_018116.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0930
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06039837).

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.104C>T	p.Ala35Val	missense	Exon 2 of 14	NP_060586.2
	MSTO1	NM_001256532.1		c.104C>T	p.Ala35Val	missense	Exon 2 of 14	NP_001243461.1	Q9BUK6-2
	MSTO1	NM_001350772.1		c.104C>T	p.Ala35Val	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.104C>T	p.Ala35Val	missense	Exon 2 of 14	ENSP00000245564.3	Q9BUK6-1
	MSTO1	ENST00000368341.8	TSL:2	c.104C>T	p.Ala35Val	missense	Exon 2 of 13	ENSP00000357325.4	Q9BUK6-7
	MSTO1	ENST00000490743.5	TSL:1	n.104C>T		non_coding_transcript_exon	Exon 2 of 13	ENSP00000476353.1	Q9BUK6-4

Frequencies

GnomAD3 genomes AF: 0.00000734 AC: 1 AN: 136192 Hom.: 0 Cov.: 20

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: 0.0000158

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 83938 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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000559 AC: 4 AN: 714974 Hom.: 0 Cov.: 9 AF XY: 0.00000271 AC XY: 1 AN XY: 368350

⚠️ 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: 18718

American (AMR) AF: 0.00 AC: 0 AN: 32142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17852

East Asian (EAS) AF: 0.00 AC: 0 AN: 32704

South Asian (SAS) AF: 0.00 AC: 0 AN: 59130

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31696

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2600

European-Non Finnish (NFE) AF: 0.00000825 AC: 4 AN: 484642

Other (OTH) AF: 0.00 AC: 0 AN: 35490

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0236461), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000734 AC: 1 AN: 136192 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 65396

African (AFR) AF: 0.00 AC: 0 AN: 35430

American (AMR) AF: 0.00 AC: 0 AN: 13712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3316

East Asian (EAS) AF: 0.00 AC: 0 AN: 4552

South Asian (SAS) AF: 0.00 AC: 0 AN: 3618

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9220

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.0000158 AC: 1 AN: 63448

Other (OTH) AF: 0.00 AC: 0 AN: 1766

Alfa AF: 0.00 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	0.078
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.0083	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.093
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.021
Sift	Benign	1.0	T
Sift4G	Benign	0.31	T
Polyphen		0.098	B
Vest4		0.075
MutPred		0.30		Loss of disorder (P = 0.0604)
MVP		0.22
MPC		2.0
ClinPred		0.091	T
GERP RS		0.073
PromoterAI		0.012	Neutral
Varity_R		0.016
gMVP		0.23
Mutation Taster		=91/9	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: rs762447527; hg19: chr1-155580235;