1-155610249-A-G

Variant names:

• chr1-155610249-A-G
• rs955399709
• NM_018116.4:c.1A>G

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_Strong PS1_Moderate PM2

The NM_018116.4(MSTO1):​c.1A>G​(p.Met1?) variant causes a start lost change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 28)
• Consequence: MSTO1 NM_018116.4 start_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.73

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]

ENSG00000232519 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PVS1: Start lost variant, next in-frame start position is after 5 pathogenic variants. Next in-frame start position is after 70 codons. Genomic position: 155610548. Lost 0.121 part of the original CDS.
• PS1: Another start lost variant in NM_018116.4 (MSTO1) was described as [Likely_pathogenic] in ClinVar as 2229213
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSTO1	NM_018116.4	c.1A>G	p.Met1?	start_lost	Exon 1 of 14	ENST00000245564.8	NP_060586.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSTO1	ENST00000245564.8	c.1A>G	p.Met1?	start_lost	Exon 1 of 14	1	NM_018116.4	ENSP00000245564.3
MSTO1	ENST00000368341.8	c.1A>G	p.Met1?	start_lost	Exon 1 of 13	2		ENSP00000357325.4

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Cov.: 6

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0074	.;T;.
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Uncertain	0.086	D
MetaRNN	Uncertain	0.61	D;D;D
MetaSVM	Benign	-0.87	T
PROVEAN	Benign	-1.6	.;N;N
REVEL	Uncertain	0.29
Sift	Pathogenic	0.0	.;D;D
Sift4G	Pathogenic	0.0	.;D;D
Polyphen		0.96	.;D;.
Vest4		0.84, 0.82
MutPred		0.48		Loss of disorder (P = 0.1941);Loss of disorder (P = 0.1941);Loss of disorder (P = 0.1941);
MVP		0.36
ClinPred		1.0	D
GERP RS		3.3
Varity_R		0.95
gMVP		0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs955399709; hg19: chr1-155580040;