1-155610292-A-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 Uncertain_significance. Variant got 4 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSTO1	NM_018116.4	c.44A>T	p.His15Leu	missense_variant	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.44A>T	p.His15Leu	missense_variant	Exon 1 of 14	1	NM_018116.4	ENSP00000245564.3
MSTO1	ENST00000368341.8	c.44A>T	p.His15Leu	missense_variant	Exon 1 of 13	2		ENSP00000357325.4

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000290

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;D
M_CAP	Benign	0.033	D
MetaRNN	Pathogenic	0.88	D;D;D
MetaSVM	Benign	-0.49	T
MutationAssessor	Uncertain	2.7	.;M;M
PrimateAI	Pathogenic	0.92	D
PROVEAN	Pathogenic	-7.4	.;D;D
REVEL	Uncertain	0.55
Sift	Uncertain	0.013	.;D;D
Sift4G	Uncertain	0.021	.;D;D
Polyphen		1.0	.;D;.
Vest4		0.70, 0.69
MutPred		0.75		Loss of MoRF binding (P = 0.3328);Loss of MoRF binding (P = 0.3328);Loss of MoRF binding (P = 0.3328);
MVP		0.71
MPC		4.0
ClinPred		0.99	D
GERP RS		3.3
Varity_R		0.40
gMVP		0.72

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-155580083;