chr1-155610528-A-C

Variant names:

• chr1-155610528-A-C
• NM_018116.4:c.188A>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_018116.4(MSTO1):​c.188A>C​(p.Tyr63Ser) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 18)
• Consequence: MSTO1 NM_018116.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.68

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]

LOC105371452 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.896

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSTO1	NM_018116.4	c.188A>C	p.Tyr63Ser	missense_variant	Exon 2 of 14	ENST00000245564.8	NP_060586.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSTO1	ENST00000245564.8	c.188A>C	p.Tyr63Ser	missense_variant	Exon 2 of 14	1	NM_018116.4	ENSP00000245564.3
MSTO1	ENST00000368341.8	c.188A>C	p.Tyr63Ser	missense_variant	Exon 2 of 13	2		ENSP00000357325.4

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD4 exome Cov.: 11

GnomAD4 genome Cov.: 18

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Feb 18, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.188A>C (p.Y63S) alteration is located in exon 2 (coding exon 2) of the MSTO1 gene. This alteration results from an A to C substitution at nucleotide position 188, causing the tyrosine (Y) at amino acid position 63 to be replaced by a serine (S). Based on data from the Genome Aggregation Database (gnomAD), the MSTO1 c.188A>C alteration was not observed. This amino acid position is highly conserved in available vertebrate species. The in silico prediction for the p.Y63S alteration is inconclusive. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	.;T;.
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.86	D;T;D
M_CAP	Benign	0.047	D
MetaRNN	Pathogenic	0.90	D;D;D
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Pathogenic	3.1	.;M;M
PrimateAI	Uncertain	0.79	T
PROVEAN	Pathogenic	-6.0	.;D;D
REVEL	Pathogenic	0.71
Sift	Uncertain	0.0030	.;D;D
Sift4G	Uncertain	0.023	.;D;D
Polyphen		1.0	.;D;.
Vest4		0.77, 0.73
MutPred		0.78		Gain of disorder (P = 0.0042);Gain of disorder (P = 0.0042);Gain of disorder (P = 0.0042);
MVP		0.85
MPC		3.6
ClinPred		0.99	D
GERP RS		3.2
Varity_R		0.48
gMVP		0.78

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-155580319;