Variant 8-17655975-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001363059.2(MTUS1):c.2996A>G(p.Glu999Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00806 in 1,614,248 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0073 ( 13 hom., cov: 32)

Exomes 𝑓: 0.0081 ( 71 hom. )

Consequence

MTUS1
NM_001363059.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.45

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 made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037794113).

BP6

Variant 8-17655975-T-C is Benign according to our data. Variant chr8-17655975-T-C is described in ClinVar as [Benign]. Clinvar id is 777177.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTUS1	NM_001363059.2 linkuse as main transcript	c.2996A>G	p.Glu999Gly	missense_variant	9/15	ENST00000693296.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTUS1	ENST00000693296.1 linkuse as main transcript	c.2996A>G	p.Glu999Gly	missense_variant	9/15		NM_001363059.2		Q9ULD2-1

Frequencies

GnomAD3 genomes

AF:

0.00731

AC:

1113

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000892

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.00951

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.0139

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0122

Gnomad OTH

AF:

0.00716

GnomAD3 exomes

AF:

0.00829

AC:

2070

AN:

249574

Hom.:

AF XY:

0.00849

AC XY:

1150

AN XY:

135406

show subpopulations

Gnomad AFR exome

AF:

0.000710

Gnomad AMR exome

AF:

0.00310

Gnomad ASJ exome

AF:

0.00864

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00248

Gnomad FIN exome

AF:

0.0170

Gnomad NFE exome

AF:

0.0121

Gnomad OTH exome

AF:

0.00923

GnomAD4 exome

AF:

0.00814

AC:

11903

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00827

AC XY:

6016

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.00295

Gnomad4 ASJ exome

AF:

0.00911

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.00267

Gnomad4 FIN exome

AF:

0.0178

Gnomad4 NFE exome

AF:

0.00889

Gnomad4 OTH exome

AF:

0.00666

GnomAD4 genome

AF:

0.00731

AC:

1114

AN:

152364

Hom.:

Cov.:

AF XY:

0.00692

AC XY:

516

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.000890

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.00951

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.0139

Gnomad4 NFE

AF:

0.0122

Gnomad4 OTH

AF:

0.00709

Alfa

AF:

0.0109

Hom.:

Bravo

AF:

0.00559

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00493

AC:

ESP6500AA

AF:

0.00213

AC:

ESP6500EA

AF:

0.00922

AC:

ExAC

AF:

0.00911

AC:

1101

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00911

EpiControl

AF:

0.0108

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

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

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.93

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

MetaRNN

Benign

0.0038

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

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.0

.;.;.;.;M;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-4.0

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

REVEL

Benign

0.21

Sift

Uncertain

0.0090

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

Sift4G

Uncertain

0.018

D;D;D;D;D;D;D

Polyphen

0.73, 0.25, 0.41

.;P;B;B;P;P;.

Vest4

0.25

MVP

0.67

ClinPred

0.035

GERP RS

5.1

Varity_R

0.31

gMVP

0.23

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over