Genetic Variant MTUS1:p.Lys453Thr (chr8-17754450-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001363059.2(MTUS1):c.1358A>C(p.Lys453Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0381 in 1,614,176 control chromosomes in the GnomAD database, including 2,793 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.072 ( 725 hom., cov: 33)

Exomes 𝑓: 0.035 ( 2068 hom. )

Consequence

MTUS1
NM_001363059.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.43

Publications

11 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:

ENSG00000301996 (HGNC:):

ENSG00000301996 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012432039).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTUS1	NM_001363059.2 link	c.1358A>C	p.Lys453Thr	missense_variant	Exon 2 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.1358A>C	p.Lys453Thr	missense_variant	Exon 2 of 15		NM_001363059.2	ENSP00000509719.1		Q9ULD2-1

Frequencies

GnomAD3 genomes

AF:

0.0721

AC:

10972

AN:

152178

Hom.:

720

Cov.:

show subpopulations

Gnomad AFR

AF:

0.163

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0532

Gnomad ASJ

AF:

0.00289

Gnomad EAS

AF:

0.203

Gnomad SAS

AF:

0.0147

Gnomad FIN

AF:

0.0419

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0250

Gnomad OTH

AF:

0.0597

GnomAD2 exomes

AF:

0.0464

AC:

11579

AN:

249570

AF XY:

0.0419

show subpopulations

Gnomad AFR exome

AF:

0.167

Gnomad AMR exome

AF:

0.0482

Gnomad ASJ exome

AF:

0.00486

Gnomad EAS exome

AF:

0.184

Gnomad FIN exome

AF:

0.0401

Gnomad NFE exome

AF:

0.0223

Gnomad OTH exome

AF:

0.0308

GnomAD4 exome

AF:

0.0345

AC:

50485

AN:

1461880

Hom.:

2068

Cov.:

AF XY:

0.0332

AC XY:

24154

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.168

AC:

5618

AN:

33478

American (AMR)

AF:

0.0487

AC:

2176

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00398

AC:

104

AN:

26136

East Asian (EAS)

AF:

0.221

AC:

8761

AN:

39700

South Asian (SAS)

AF:

0.0128

AC:

1108

AN:

86256

European-Finnish (FIN)

AF:

0.0395

AC:

2108

AN:

53418

Middle Eastern (MID)

AF:

0.0198

AC:

114

AN:

5768

European-Non Finnish (NFE)

AF:

0.0252

AC:

28039

AN:

1112004

Other (OTH)

AF:

0.0407

AC:

2457

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

3278

6557

9835

13114

16392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1266

2532

3798

5064

6330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0722

AC:

11000

AN:

152296

Hom.:

725

Cov.:

AF XY:

0.0731

AC XY:

5446

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.163

AC:

6779

AN:

41544

American (AMR)

AF:

0.0530

AC:

811

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00289

AC:

AN:

3466

East Asian (EAS)

AF:

0.203

AC:

1054

AN:

5180

South Asian (SAS)

AF:

0.0147

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0419

AC:

445

AN:

10622

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0250

AC:

1700

AN:

68030

Other (OTH)

AF:

0.0595

AC:

126

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

483

967

1450

1934

2417

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

122

244

366

488

610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0399

Hom.:

1263

Bravo

AF:

0.0772

TwinsUK

AF:

0.0235

AC:

ALSPAC

AF:

0.0249

AC:

ESP6500AA

AF:

0.157

AC:

588

ESP6500EA

AF:

0.0286

AC:

236

ExAC

AF:

0.0470

AC:

5678

Asia WGS

AF:

0.0830

AC:

289

AN:

3478

EpiCase

AF:

0.0236

EpiControl

AF:

0.0219

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.57

CADD

Benign

8.8

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.020

.;T;.

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.64

T;T;.

MetaRNN

Benign

0.0012

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.9

L;L;L

PhyloP100

1.4

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.81

N;N;N

REVEL

Benign

0.020

Sift

Benign

0.15

T;T;T

Sift4G

Benign

0.17

T;T;T

Polyphen

0.041

B;B;B

Vest4

0.12

ClinPred

0.0073

GERP RS

2.5

Varity_R

0.069

gMVP

0.090

Mutation Taster

=95/5

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over