Genetic Variant NM_001033602.4:c.3295G>C (chr13-29480260-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001033602.4(MTUS2):c.3295G>C(p.Glu1099Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000772 in 1,553,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 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: 0.0000043 ( 0 hom. )

Consequence

MTUS2
NM_001033602.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.14

Publications

0 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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.122668296).

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.3295G>C	p.Glu1099Gln	missense	Exon 10 of 16	NP_001028774.3	Q5JR59-2
MTUS2	NM_001384605.1		c.3295G>C	p.Glu1099Gln	missense	Exon 10 of 16	NP_001371534.1	Q5JR59-2
MTUS2	NM_001384606.1		c.3295G>C	p.Glu1099Gln	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.3295G>C	p.Glu1099Gln	missense	Exon 10 of 16	ENSP00000483729.2	Q5JR59-2
MTUS2	ENST00000380808.6	TSL:1	c.232G>C	p.Glu78Gln	missense	Exon 3 of 9	ENSP00000370186.2	Q5JR59-3
MTUS2	ENST00000542829.1	TSL:1	c.-39G>C		5_prime_UTR	Exon 2 of 8	ENSP00000445403.1	Q5JR59-4

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000127

AC:

AN:

157362

AF XY:

0.0000239

show subpopulations

Gnomad AFR exome

AF:

0.000126

Gnomad AMR exome

AF:

0.0000398

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:

0.00000428

AC:

AN:

1401552

Hom.:

Cov.:

AF XY:

0.00000578

AC XY:

AN XY:

691470

show subpopulations

African (AFR)

AF:

0.000126

AC:

AN:

31748

American (AMR)

AF:

0.0000277

AC:

AN:

36092

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25202

East Asian (EAS)

AF:

0.00

AC:

AN:

36030

South Asian (SAS)

AF:

0.00

AC:

AN:

79358

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5172

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1080518

Other (OTH)

AF:

0.0000172

AC:

AN:

58036

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

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

AF:

0.0000394

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41460

American (AMR)

AF:

0.000262

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000416

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

0.098

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.60

CADD

Uncertain

(source)

DANN

Uncertain

1.0

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.010

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

PhyloP100

4.1

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.9

REVEL

Benign

0.085

Sift

Benign

0.16

Sift4G

Benign

0.39

Polyphen

0.12

Vest4

0.14

MVP

0.055

ClinPred

0.42

GERP RS

5.4

Mutation Taster

=92/8

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over