1-155610461-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018116.4(MSTO1):c.121C>A(p.Pro41Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (65 hom., cov: 18)
  • Exomes 𝑓: 0.0024 (48 hom.)
  • Failed GnomAD Quality Control
• Consequence: MSTO1 NM_018116.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.406

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017667115).
• BP6: Variant 1-155610461-C-A is Benign according to our data. Variant chr1-155610461-C-A is described in ClinVar as [Benign]. Clinvar id is 1288287.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSTO1	NM_018116.4	c.121C>A	p.Pro41Thr	missense_variant	2/14	ENST00000245564.8
LOC105371452	XR_922171.2	n.77-569G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSTO1	ENST00000245564.8	c.121C>A	p.Pro41Thr	missense_variant	2/14	1	NM_018116.4	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 2192 AN: 130756 Hom.: 65 Cov.: 18 FAILED QC

Gnomad AFR AF: 0.0630

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00424

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000453

Gnomad SAS AF: 0.000591

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00658

Gnomad NFE AF: 0.000227

Gnomad OTH AF: 0.0129

GnomAD3 exomes AF: 0.00575 AC: 479 AN: 83238 Hom.: 12 AF XY: 0.00448 AC XY: 193 AN XY: 43048

Gnomad AFR exome AF: 0.0691

Gnomad AMR exome AF: 0.00284

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000210

Gnomad SAS exome AF: 0.000339

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000101

Gnomad OTH exome AF: 0.00150

GnomAD4 exome AF: 0.00238 AC: 1627 AN: 684694 Hom.: 48 Cov.: 9 AF XY: 0.00197 AC XY: 699 AN XY: 354844

Gnomad4 AFR exome AF: 0.0688

Gnomad4 AMR exome AF: 0.00353

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000122

Gnomad4 SAS exome AF: 0.000540

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000944

Gnomad4 OTH exome AF: 0.00518

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0168 AC: 2193 AN: 130864 Hom.: 65 Cov.: 18 AF XY: 0.0158 AC XY: 985 AN XY: 62480

Gnomad4 AFR AF: 0.0628

Gnomad4 AMR AF: 0.00423

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000454

Gnomad4 SAS AF: 0.000296

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000227

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00108 Hom.: 2

ExAC AF: 0.00183 AC: 165

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.52
Cadd	Benign	6.7
Dann	Benign	0.81
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.74	T;T;T
MetaRNN	Benign	0.0018	T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Uncertain	0.55	T
Polyphen		0.83	.;P;.
Vest4		0.11, 0.13
MVP		0.14
MPC		2.1
ClinPred		0.029	T
GERP RS		-1.5
Varity_R		0.039
gMVP		0.24

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: rs553985742; hg19: chr1-155580252; COSMIC: COSV55471878; COSMIC: COSV55471878;