Variant 8-17754450-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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:

MTUS1 (HGNC:):

MTUS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MTUS1	NM_001363059.2 linkuse as main transcript	c.1358A>C	p.Lys453Thr	missense_variant	2/15	ENST00000693296.1	NP_001349988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTUS1	ENST00000693296.1 linkuse as main transcript	c.1358A>C	p.Lys453Thr	missense_variant	2/15		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

GnomAD3 exomes

AF:

0.0464

AC:

11579

AN:

249570

Hom.:

634

AF XY:

0.0419

AC XY:

5670

AN XY:

135402

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 SAS exome

AF:

0.0127

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

Gnomad4 AFR exome

AF:

0.168

Gnomad4 AMR exome

AF:

0.0487

Gnomad4 ASJ exome

AF:

0.00398

Gnomad4 EAS exome

AF:

0.221

Gnomad4 SAS exome

AF:

0.0128

Gnomad4 FIN exome

AF:

0.0395

Gnomad4 NFE exome

AF:

0.0252

Gnomad4 OTH exome

AF:

0.0407

GnomAD4 genome

AF:

0.0722

AC:

11000

AN:

152296

Hom.:

725

Cov.:

AF XY:

0.0731

AC XY:

5446

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.163

Gnomad4 AMR

AF:

0.0530

Gnomad4 ASJ

AF:

0.00289

Gnomad4 EAS

AF:

0.203

Gnomad4 SAS

AF:

0.0147

Gnomad4 FIN

AF:

0.0419

Gnomad4 NFE

AF:

0.0250

Gnomad4 OTH

AF:

0.0595

Alfa

AF:

0.0336

Hom.:

484

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

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

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

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over