Variant 13-29480345-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001033602.4(MTUS2):c.3380G>A(p.Arg1127Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000024 in 1,540,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

MTUS2
NM_001033602.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.37

Variant links:

Genes affected

MTUS2 (HGNC:20595): (microtubule associated scaffold protein 2) Enables microtubule binding activity and protein homodimerization activity. Part of nucleus. Colocalizes with centrosome and cytoplasmic microtubule. [provided by Alliance of Genome Resources, Apr 2022]

MTUS2 links:

MTUS2-AS1 (HGNC:40924): (MTUS2 antisense RNA 1)

MTUS2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.023673922).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTUS2	NM_001033602.4 linkuse as main transcript	c.3380G>A	p.Arg1127Gln	missense_variant	10/16	ENST00000612955.6	NP_001028774.3
MTUS2-AS1	NR_046378.1 linkuse as main transcript	n.690-3406C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTUS2	ENST00000612955.6 linkuse as main transcript	c.3380G>A	p.Arg1127Gln	missense_variant	10/16	5	NM_001033602.4	ENSP00000483729		Q5JR59-2
MTUS2-AS1	ENST00000323380.7 linkuse as main transcript	n.1568-3406C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000469

AC:

AN:

149200

Hom.:

AF XY:

0.0000510

AC XY:

AN XY:

78470

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000407

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000263

Gnomad SAS exome

AF:

0.0000506

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000341

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000223

AC:

AN:

1388186

Hom.:

Cov.:

AF XY:

0.0000132

AC XY:

AN XY:

683110

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000305

Gnomad4 SAS exome

AF:

0.0000261

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000158

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.0000179

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2022

The c.3410G>A (p.R1137Q) alteration is located in exon 8 (coding exon 8) of the MTUS2 gene. This alteration results from a G to A substitution at nucleotide position 3410, causing the arginine (R) at amino acid position 1137 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.089

LIST_S2

Benign

0.76

T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.024

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-2.3

.;N;N

REVEL

Benign

0.028

Sift

Benign

0.14

.;T;T

Sift4G

Benign

0.13

T;T;T

Polyphen

0.055

.;B;.

Vest4

0.19

MVP

0.030

ClinPred

0.088

GERP RS

3.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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