8-17653257-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001363059.2(MTUS1):c.3313G>C(p.Glu1105Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00764 in 1,557,832 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0077 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0076 ( 61 hom. )

Consequence

MTUS1
NM_001363059.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.82

Publications

13 publications found

Variant links:

Genes affected

MTUS1 (HGNC:29789): (microtubule associated scaffold protein 1) This gene encodes a protein which contains a C-terminal domain able to interact with the angiotension II (AT2) receptor and a large coiled-coil region allowing dimerization. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. One of the transcript variants has been shown to encode a mitochondrial protein that acts as a tumor suppressor and partcipates in AT2 signaling pathways. Other variants may encode nuclear or transmembrane proteins but it has not been determined whether they also participate in AT2 signaling pathways. [provided by RefSeq, Jul 2008]

MTUS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007748425).

BP6

Variant 8-17653257-C-G is Benign according to our data. Variant chr8-17653257-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2658445.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00763 (10720/1405544) while in subpopulation MID AF = 0.0221 (125/5660). AF 95% confidence interval is 0.0189. There are 61 homozygotes in GnomAdExome4. There are 5272 alleles in the male GnomAdExome4 subpopulation. Median coverage is 29. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 61 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTUS1	NM_001363059.2 link	c.3313G>C	p.Glu1105Gln	missense_variant	Exon 12 of 15	ENST00000693296.1	NP_001349988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTUS1	ENST00000693296.1 link	c.3313G>C	p.Glu1105Gln	missense_variant	Exon 12 of 15		NM_001363059.2	ENSP00000509719.1		Q9ULD2-1

Frequencies

GnomAD3 genomes

AF:

0.00766

AC:

1166

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00794

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00635

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.00192

Gnomad SAS

AF:

0.00871

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.00950

Gnomad OTH

AF:

0.00813

GnomAD2 exomes

AF:

0.00594

AC:

1092

AN:

183926

AF XY:

0.00579

show subpopulations

Gnomad AFR exome

AF:

0.00692

Gnomad AMR exome

AF:

0.00470

Gnomad ASJ exome

AF:

0.00543

Gnomad EAS exome

AF:

0.00224

Gnomad FIN exome

AF:

0.000560

Gnomad NFE exome

AF:

0.00786

Gnomad OTH exome

AF:

0.00750

GnomAD4 exome

AF:

0.00763

AC:

10720

AN:

1405544

Hom.:

Cov.:

AF XY:

0.00756

AC XY:

5272

AN XY:

696984

show subpopulations

African (AFR)

AF:

0.00626

AC:

193

AN:

30852

American (AMR)

AF:

0.00504

AC:

148

AN:

29354

Ashkenazi Jewish (ASJ)

AF:

0.00485

AC:

120

AN:

24738

East Asian (EAS)

AF:

0.00217

AC:

AN:

38720

South Asian (SAS)

AF:

0.00592

AC:

458

AN:

77386

European-Finnish (FIN)

AF:

0.000902

AC:

AN:

52100

Middle Eastern (MID)

AF:

0.0221

AC:

125

AN:

5660

European-Non Finnish (NFE)

AF:

0.00830

AC:

9034

AN:

1088490

Other (OTH)

AF:

0.00877

AC:

511

AN:

58244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.437

Heterozygous variant carriers

463

925

1388

1850

2313

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00772

AC:

1175

AN:

152288

Hom.:

Cov.:

AF XY:

0.00739

AC XY:

550

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.00809

AC:

336

AN:

41558

American (AMR)

AF:

0.00634

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00432

AC:

AN:

3470

East Asian (EAS)

AF:

0.00193

AC:

AN:

5186

South Asian (SAS)

AF:

0.00913

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.000565

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00950

AC:

646

AN:

68020

Other (OTH)

AF:

0.00805

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

129

194

258

323

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00892

Hom.:

Bravo

AF:

0.00783

TwinsUK

AF:

0.0105

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.00745

AC:

ESP6500EA

AF:

0.00785

AC:

ExAC

AF:

0.00474

AC:

570

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

MTUS1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.010

.;.;.;.;T;.;.

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

D;D;D;D;D;.;D

MetaRNN

Benign

0.0077

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.86

.;.;.;.;L;.;.

PhyloP100

4.8

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.8

N;N;N;N;N;N;.

REVEL

Benign

0.19

Sift

Benign

0.67

T;T;T;T;T;T;.

Sift4G

Benign

0.47

T;T;T;T;T;T;T

Polyphen

0.94, 1.0, 0.97

.;P;D;D;P;P;.

Vest4

0.52

MVP

0.57

ClinPred

0.039

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.23

gMVP

0.37

Mutation Taster

=97/3

polymorphism

(source)

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

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8-17653257-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over