Genetic Variant MTUS2:p.Thr947Met (chr13-29324646-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001033602.4(MTUS2):c.2840C>T(p.Thr947Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0303 in 1,594,210 control chromosomes in the GnomAD database, including 879 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.025 ( 69 hom., cov: 34)

Exomes 𝑓: 0.031 ( 810 hom. )

Consequence

MTUS2
NM_001033602.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.524

Publications

13 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024681985).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.025 (3813/152308) while in subpopulation NFE AF = 0.0346 (2355/68024). AF 95% confidence interval is 0.0335. There are 69 homozygotes in GnomAd4. There are 1852 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 69 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTUS2	NM_001033602.4 link	c.2840C>T	p.Thr947Met	missense_variant	Exon 7 of 16	ENST00000612955.6	NP_001028774.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTUS2	ENST00000612955.6 link	c.2840C>T	p.Thr947Met	missense_variant	Exon 7 of 16	5	NM_001033602.4	ENSP00000483729.2		Q5JR59-2

Frequencies

GnomAD3 genomes

AF:

0.0251

AC:

3814

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00820

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0198

Gnomad ASJ

AF:

0.0715

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0261

Gnomad FIN

AF:

0.0343

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0346

Gnomad OTH

AF:

0.0310

GnomAD2 exomes

AF:

0.0279

AC:

6132

AN:

219886

AF XY:

0.0284

show subpopulations

Gnomad AFR exome

AF:

0.00880

Gnomad AMR exome

AF:

0.0147

Gnomad ASJ exome

AF:

0.0768

Gnomad EAS exome

AF:

0.000123

Gnomad FIN exome

AF:

0.0344

Gnomad NFE exome

AF:

0.0336

Gnomad OTH exome

AF:

0.0307

GnomAD4 exome

AF:

0.0308

AC:

44444

AN:

1441902

Hom.:

810

Cov.:

AF XY:

0.0308

AC XY:

22025

AN XY:

714902

show subpopulations

African (AFR)

AF:

0.00872

AC:

290

AN:

33246

American (AMR)

AF:

0.0148

AC:

618

AN:

41774

Ashkenazi Jewish (ASJ)

AF:

0.0755

AC:

1933

AN:

25616

East Asian (EAS)

AF:

0.0000509

AC:

AN:

39264

South Asian (SAS)

AF:

0.0266

AC:

2189

AN:

82408

European-Finnish (FIN)

AF:

0.0347

AC:

1815

AN:

52366

Middle Eastern (MID)

AF:

0.0360

AC:

207

AN:

5744

European-Non Finnish (NFE)

AF:

0.0323

AC:

35548

AN:

1101692

Other (OTH)

AF:

0.0308

AC:

1842

AN:

59792

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

1907

3814

5720

7627

9534

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1314

2628

3942

5256

6570

<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:

0.0250

AC:

3813

AN:

152308

Hom.:

Cov.:

AF XY:

0.0249

AC XY:

1852

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.00825

AC:

343

AN:

41570

American (AMR)

AF:

0.0198

AC:

303

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0715

AC:

248

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5188

South Asian (SAS)

AF:

0.0255

AC:

123

AN:

4824

European-Finnish (FIN)

AF:

0.0343

AC:

364

AN:

10608

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0346

AC:

2355

AN:

68024

Other (OTH)

AF:

0.0307

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

196

392

589

785

981

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0311

Hom.:

268

Bravo

AF:

0.0235

TwinsUK

AF:

0.0348

AC:

129

ALSPAC

AF:

0.0337

AC:

130

ESP6500AA

AF:

0.00829

AC:

ESP6500EA

AF:

0.0376

AC:

308

ExAC

AF:

0.0258

AC:

3114

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.81

MetaRNN

Benign

0.0025

MetaSVM

Benign

-0.96

PhyloP100

0.52

PrimateAI

Benign

0.30

Sift4G

Uncertain

0.011

Vest4

0.042

ClinPred

0.018

GERP RS

3.9

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over