Genetic Variant NM_001033602.4:c.3307C>T (chr13-29480272-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001033602.4(MTUS2):c.3307C>T(p.Arg1103Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000285 in 1,402,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

MTUS2
NM_001033602.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0830

Publications

2 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3466484).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033602.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MTUS2	NM_001033602.4	MANE Select	c.3307C>T	p.Arg1103Trp	missense	Exon 10 of 16	NP_001028774.3	Q5JR59-2
MTUS2	NM_001384605.1		c.3307C>T	p.Arg1103Trp	missense	Exon 10 of 16	NP_001371534.1	Q5JR59-2
MTUS2	NM_001384606.1		c.3307C>T	p.Arg1103Trp	missense	Exon 9 of 15	NP_001371535.1	Q5JR59-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MTUS2	ENST00000612955.6	TSL:5 MANE Select	c.3307C>T	p.Arg1103Trp	missense	Exon 10 of 16	ENSP00000483729.2	Q5JR59-2
MTUS2	ENST00000380808.6	TSL:1	c.244C>T	p.Arg82Trp	missense	Exon 3 of 9	ENSP00000370186.2	Q5JR59-3
MTUS2	ENST00000542829.1	TSL:1	c.-27C>T		5_prime_UTR	Exon 2 of 8	ENSP00000445403.1	Q5JR59-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

158416

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000285

AC:

AN:

1402012

Hom.:

Cov.:

AF XY:

0.00000434

AC XY:

AN XY:

691746

show subpopulations

African (AFR)

AF:

0.0000315

AC:

AN:

31796

American (AMR)

AF:

0.00

AC:

AN:

36132

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25206

East Asian (EAS)

AF:

0.00

AC:

AN:

36084

South Asian (SAS)

AF:

0.00

AC:

AN:

79368

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49428

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5020

European-Non Finnish (NFE)

AF:

0.00000278

AC:

AN:

1080904

Other (OTH)

AF:

0.00

AC:

AN:

58074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000266

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.030

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.85

M_CAP

Benign

0.046

MetaRNN

Benign

0.35

MetaSVM

Benign

-0.89

PhyloP100

0.083

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-6.7

REVEL

Benign

0.21

Sift

Uncertain

0.0090

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.56

MVP

0.14

ClinPred

1.0

GERP RS

2.4

Mutation Taster

=87/13

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over