1-155610262-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS1

The NM_018116.4(MSTO1):c.14C>T(p.Ala5Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00157 in 764,272 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0016 (2 hom.)
• Consequence: MSTO1 NM_018116.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.60

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00959298).
• BP6: Variant 1-155610262-C-T is Benign according to our data. Variant chr1-155610262-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2456933.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00151 (228/151284) while in subpopulation NFE AF= 0.00185 (125/67750). AF 95% confidence interval is 0.00158. There are 0 homozygotes in gnomad4. There are 100 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSTO1	NM_018116.4	c.14C>T	p.Ala5Val	missense_variant	1/14	ENST00000245564.8
LOC105371452	XR_922171.2	n.77-370G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSTO1	ENST00000245564.8	c.14C>T	p.Ala5Val	missense_variant	1/14	1	NM_018116.4	P1
	ENST00000456382.2	n.103+16G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00151 AC: 228 AN: 151170 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.000414

Gnomad AMI AF: 0.0275

Gnomad AMR AF: 0.000526

Gnomad ASJ AF: 0.0122

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00170

Gnomad FIN AF: 0.0000953

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00184

Gnomad OTH AF: 0.000968

GnomAD3 exomes AF: 0.00134 AC: 154 AN: 114550 Hom.: 0 AF XY: 0.00131 AC XY: 80 AN XY: 61184

Gnomad AFR exome AF: 0.000503

Gnomad AMR exome AF: 0.000433

Gnomad ASJ exome AF: 0.0128

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000176

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00190

Gnomad OTH exome AF: 0.00171

GnomAD4 exome AF: 0.00159 AC: 974 AN: 612988 Hom.: 2 Cov.: 8 AF XY: 0.00158 AC XY: 503 AN XY: 317660

Gnomad4 AFR exome AF: 0.000694

Gnomad4 AMR exome AF: 0.000547

Gnomad4 ASJ exome AF: 0.0104

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000545

Gnomad4 FIN exome AF: 0.0000869

Gnomad4 NFE exome AF: 0.00174

Gnomad4 OTH exome AF: 0.00187

GnomAD4 genome AF: 0.00151 AC: 228 AN: 151284 Hom.: 0 Cov.: 28 AF XY: 0.00135 AC XY: 100 AN XY: 73878

Gnomad4 AFR AF: 0.000412

Gnomad4 AMR AF: 0.000526

Gnomad4 ASJ AF: 0.0122

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00170

Gnomad4 FIN AF: 0.0000953

Gnomad4 NFE AF: 0.00185

Gnomad4 OTH AF: 0.000958

Alfa AF: 0.000903 Hom.: 0

Bravo AF: 0.00168

ExAC AF: 0.000974 AC: 106

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Inborn genetic diseases Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 16, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2023

MSTO1: PP2, BS1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	18
Dann	Pathogenic	1.0
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.71	T;T;T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.0096	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.94	N;N;N;N
PrimateAI	Uncertain	0.77	T
Polyphen		0.19	.;B;.
Vest4		0.20, 0.12
MVP		0.31
MPC		1.8
ClinPred		0.0089	T
GERP RS		3.3
Varity_R		0.039
gMVP		0.32

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

LitVar

Other links and lift over

dbSNP: rs141537147; hg19: chr1-155580053;