rs553985742

Variant names:

• chr1-155610461-C-A
• rs553985742
• NM_018116.4:c.121C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-155610461-C-A
• chr1-155610461-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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. 15/21 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.406
• Publications: 2 publications found

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]

MSTO1 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Broad Center for Mendelian Genomics, Ambry Genetics

LOC105371452 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1288287.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0656 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018116.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSTO1	NM_018116.4	MANE Select	c.121C>A	p.Pro41Thr	missense	Exon 2 of 14	NP_060586.2
	MSTO1	NM_001256532.1		c.121C>A	p.Pro41Thr	missense	Exon 2 of 14	NP_001243461.1	Q9BUK6-2
	MSTO1	NM_001350772.1		c.121C>A	p.Pro41Thr	missense	Exon 2 of 14	NP_001337701.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSTO1	ENST00000245564.8	TSL:1 MANE Select	c.121C>A	p.Pro41Thr	missense	Exon 2 of 14	ENSP00000245564.3	Q9BUK6-1
	MSTO1	ENST00000368341.8	TSL:2	c.121C>A	p.Pro41Thr	missense	Exon 2 of 13	ENSP00000357325.4	Q9BUK6-7
	MSTO1	ENST00000490743.5	TSL:1	n.121C>A		non_coding_transcript_exon	Exon 2 of 13	ENSP00000476353.1	Q9BUK6-4

Frequencies

GnomAD3 genomes AF: 0.0168 AC: 2192 AN: 130756 Hom.: 65 Cov.: 18

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

GnomAD2 exomes AF: 0.00575 AC: 479 AN: 83238 AF XY: 0.00448

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 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

African (AFR) AF: 0.0688 AC: 1248 AN: 18142

American (AMR) AF: 0.00353 AC: 114 AN: 32256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17914

East Asian (EAS) AF: 0.000122 AC: 4 AN: 32682

South Asian (SAS) AF: 0.000540 AC: 32 AN: 59210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31976

Middle Eastern (MID) AF: 0.00275 AC: 7 AN: 2546

European-Non Finnish (NFE) AF: 0.0000944 AC: 43 AN: 455436

Other (OTH) AF: 0.00518 AC: 179 AN: 34532

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

African (AFR) AF: 0.0628 AC: 2096 AN: 33372

American (AMR) AF: 0.00423 AC: 56 AN: 13226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3244

East Asian (EAS) AF: 0.000454 AC: 2 AN: 4408

South Asian (SAS) AF: 0.000296 AC: 1 AN: 3380

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8784

Middle Eastern (MID) AF: 0.00709 AC: 2 AN: 282

European-Non Finnish (NFE) AF: 0.000227 AC: 14 AN: 61650

Other (OTH) AF: 0.0128 AC: 22 AN: 1724

Alfa AF: 0.00108 Hom.: 2

ExAC AF: 0.00183 AC: 165

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
DEOGEN2	Benign	0.0076	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.9	L
PhyloP100		-0.41
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.079
Sift	Benign	0.086	T
Sift4G	Benign	0.72	T
Polyphen		0.83	P
Vest4		0.11
MVP		0.14
MPC		2.1
ClinPred		0.029	T
GERP RS		-1.5
PromoterAI		-0.0063	Neutral
Varity_R		0.039
gMVP		0.24
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

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