1-155610292-A-T

Variant names:

• chr1-155610292-A-T
• rs926774989
• NM_018116.4:c.44A>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_018116.4(MSTO1):​c.44A>T​(p.His15Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 930,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. H15R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MSTO1 NM_018116.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51
• 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

ENSG00000232519 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.881

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.44A>T	p.His15Leu	missense	Exon 1 of 14	NP_060586.2
	MSTO1	NM_001256532.1		c.44A>T	p.His15Leu	missense	Exon 1 of 14	NP_001243461.1	Q9BUK6-2
	MSTO1	NM_001350772.1		c.44A>T	p.His15Leu	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.44A>T	p.His15Leu	missense	Exon 1 of 14	ENSP00000245564.3	Q9BUK6-1
	MSTO1	ENST00000368341.8	TSL:2	c.44A>T	p.His15Leu	missense	Exon 1 of 13	ENSP00000357325.4	Q9BUK6-7
	MSTO1	ENST00000490743.5	TSL:1	n.44A>T		non_coding_transcript_exon	Exon 1 of 13	ENSP00000476353.1	Q9BUK6-4

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 0.00000215 AC: 2 AN: 930416 Hom.: 0 Cov.: 12 AF XY: 0.00000428 AC XY: 2 AN XY: 466774

African (AFR) AF: 0.00 AC: 0 AN: 21630

American (AMR) AF: 0.00 AC: 0 AN: 26092

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16888

East Asian (EAS) AF: 0.00 AC: 0 AN: 36048

South Asian (SAS) AF: 0.00 AC: 0 AN: 60228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2850

European-Non Finnish (NFE) AF: 0.00000290 AC: 2 AN: 689366

Other (OTH) AF: 0.00 AC: 0 AN: 41768

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	26
DANN	Benign	0.95
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.033	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Benign	-0.49	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		1.5
PrimateAI	Pathogenic	0.92	D
PROVEAN	Pathogenic	-7.4	D
REVEL	Uncertain	0.55
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.021	D
Polyphen		1.0	D
Vest4		0.70
MutPred		0.75		Loss of MoRF binding (P = 0.3328)
MVP		0.71
MPC		4.0
ClinPred		0.99	D
GERP RS		3.3
PromoterAI		-0.059	Neutral
Varity_R		0.40
gMVP		0.72
Mutation Taster		=72/28	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: rs926774989; hg19: chr1-155580083;