NM_018116.4:c.154C>A

Variant names:

• chr1-155610494-C-A
• NM_018116.4:c.154C>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong

The NM_018116.4(MSTO1):​c.154C>A​(p.Arg52Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R52G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 16)
  • Exomes 𝑓: 0.0000056 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MSTO1 NM_018116.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.47

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 4 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.972

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSTO1	NM_018116.4	c.154C>A	p.Arg52Ser	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.154C>A	p.Arg52Ser	missense_variant	Exon 2 of 14	1	NM_018116.4	ENSP00000245564.3
MSTO1	ENST00000368341.8	c.154C>A	p.Arg52Ser	missense_variant	Exon 2 of 13	2		ENSP00000357325.4

Frequencies

GnomAD3 genomes Cov.: 16

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000559 AC: 4 AN: 715624 Hom.: 0 Cov.: 9 AF XY: 0.00000539 AC XY: 2 AN XY: 371280

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: 0.00000831

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 16

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Apr 12, 2023

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.093	.;T;.
Eigen	Benign	0.15
Eigen_PC	Benign	-0.071
FATHMM_MKL	Benign	0.58	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Benign	0.038	D
MetaRNN	Pathogenic	0.97	D;D;D
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Pathogenic	3.3	.;M;M
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-5.1	.;D;D
REVEL	Uncertain	0.52
Sift	Uncertain	0.0030	.;D;D
Sift4G	Uncertain	0.0050	.;D;D
Polyphen		1.0	.;D;.
Vest4		0.81, 0.78
MutPred		0.94		Gain of glycosylation at R52 (P = 0.0362);Gain of glycosylation at R52 (P = 0.0362);Gain of glycosylation at R52 (P = 0.0362);
MVP		0.75
MPC		3.5
ClinPred		0.99	D
GERP RS		2.3
Varity_R		0.65
gMVP		0.85

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: chr1-155580285;