1-155610494-C-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 (★).

• 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/exons	MANE	UniProt
MSTO1	NM_018116.4	c.154C>A	p.Arg52Ser	missense_variant	2/14	ENST00000245564.8
LOC105371452	XR_922171.2	n.77-602G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSTO1	ENST00000245564.8	c.154C>A	p.Arg52Ser	missense_variant	2/14	1	NM_018116.4	P1

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

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Apr 12, 2023

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
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
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.83	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;