1-155612098-C-G

Position:

• chr1-155612098-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018116.4(MSTO1):​c.676C>G​(p.Gln226Glu) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MSTO1 NM_018116.4 missense, splice_region
• Scores: Splicing: ADA: 0.7385
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.53

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.765

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSTO1	NM_018116.4	c.676C>G	p.Gln226Glu	missense_variant, splice_region_variant	7/14	ENST00000245564.8	NP_060586.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSTO1	ENST00000245564.8	c.676C>G	p.Gln226Glu	missense_variant, splice_region_variant	7/14	1	NM_018116.4	ENSP00000245564.3
MSTO1	ENST00000368341.8	c.571C>G	p.Gln191Glu	missense_variant, splice_region_variant	6/13	2		ENSP00000357325.4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249656 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135378

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS 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: 0.00000137 AC: 2 AN: 1460772 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726712

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000447

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	.;T;.
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.022	T
MetaRNN	Pathogenic	0.77	D;D;D
MetaSVM	Benign	-0.40	T
MutationAssessor	Pathogenic	3.2	.;M;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-2.7	.;D;D
REVEL	Uncertain	0.50
Sift	Pathogenic	0.0	.;D;D
Sift4G	Pathogenic	0.0	.;D;D
Polyphen		0.47, 0.27	.;P;B
Vest4		0.77, 0.76
MutPred		0.78		Loss of catalytic residue at Q226 (P = 0.1062);Loss of catalytic residue at Q226 (P = 0.1062);.;
MVP		0.69
MPC		3.4
ClinPred		0.83	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.82
gMVP		0.87

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.74
dbscSNV1_RF	Benign	0.53
SpliceAI score (max)		0.11		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: rs1208636573; hg19: chr1-155581889;