Genetic Variant INTS13:p.Met66Thr (chr12-26936607-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_018164.3(INTS13):c.197T>C(p.Met66Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00645 in 1,611,946 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0051 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0066 ( 54 hom. )

Consequence

INTS13
NM_018164.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.87

Publications

7 publications found

Variant links:

Genes affected

INTS13 (HGNC:20174): (integrator complex subunit 13) Involved in regulation of mitotic cell cycle. Acts upstream of or within centrosome localization; mitotic spindle organization; and protein localization to nuclear envelope. Located in cytoplasm and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

INTS13 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009756386).

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INTS13	NM_018164.3 link	c.197T>C	p.Met66Thr	missense_variant	Exon 2 of 17	ENST00000261191.12	NP_060634.2	Q9NVM9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
INTS13	ENST00000261191.12 link	c.197T>C	p.Met66Thr	missense_variant	Exon 2 of 17	1	NM_018164.3	ENSP00000261191.7	Q9NVM9-1
INTS13	ENST00000544548.5 link	c.197T>C	p.Met66Thr	missense_variant	Exon 3 of 7	3		ENSP00000446183.1	F5H457
INTS13	ENST00000537336.1 link	c.197T>C	p.Met66Thr	missense_variant	Exon 2 of 4	3		ENSP00000443066.1	F5H5W1
INTS13	ENST00000538727.5 link	c.-4+1189T>C		intron_variant	Intron 1 of 3	4		ENSP00000448467.1	F8VRX9

Frequencies

GnomAD3 genomes

AF:

0.00512

AC:

780

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000917

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00864

Gnomad EAS

AF:

0.00385

Gnomad SAS

AF:

0.0168

Gnomad FIN

AF:

0.0135

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00620

Gnomad OTH

AF:

0.00525

GnomAD2 exomes

AF:

0.00706

AC:

1775

AN:

251278

AF XY:

0.00756

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00356

Gnomad ASJ exome

AF:

0.00824

Gnomad EAS exome

AF:

0.00310

Gnomad FIN exome

AF:

0.0142

Gnomad NFE exome

AF:

0.00690

Gnomad OTH exome

AF:

0.00506

GnomAD4 exome

AF:

0.00659

AC:

9619

AN:

1459620

Hom.:

Cov.:

AF XY:

0.00680

AC XY:

4941

AN XY:

726176

show subpopulations

African (AFR)

AF:

0.000957

AC:

AN:

33426

American (AMR)

AF:

0.00333

AC:

149

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00819

AC:

214

AN:

26122

East Asian (EAS)

AF:

0.00592

AC:

235

AN:

39674

South Asian (SAS)

AF:

0.0116

AC:

998

AN:

86186

European-Finnish (FIN)

AF:

0.0129

AC:

691

AN:

53360

Middle Eastern (MID)

AF:

0.00330

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00624

AC:

6929

AN:

1110040

Other (OTH)

AF:

0.00583

AC:

352

AN:

60330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

488

976

1464

1952

2440

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

268

536

804

1072

1340

<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:

0.00511

AC:

779

AN:

152326

Hom.:

Cov.:

AF XY:

0.00580

AC XY:

432

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.000914

AC:

AN:

41564

American (AMR)

AF:

0.00229

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00864

AC:

AN:

3472

East Asian (EAS)

AF:

0.00386

AC:

AN:

5186

South Asian (SAS)

AF:

0.0166

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0135

AC:

143

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00620

AC:

422

AN:

68030

Other (OTH)

AF:

0.00520

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

113

150

188

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00595

Hom.:

Bravo

AF:

0.00385

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00674

AC:

ExAC

AF:

0.00733

AC:

890

Asia WGS

AF:

0.00577

AC:

AN:

3478

EpiCase

AF:

0.00643

EpiControl

AF:

0.00717

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.59

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.049

T;.;T

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.96

D;D;D

MetaRNN

Benign

0.0098

T;T;T

MetaSVM

Benign

-1.0

PhyloP100

8.9

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.26

Sift

Uncertain

0.014

D;D;D

Sift4G

Uncertain

0.019

D;D;.

Polyphen

0.37

B;.;.

Vest4

0.64

MVP

0.043

MPC

0.94

ClinPred

0.022

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.58

gMVP

0.75

Mutation Taster

=40/60

disease causing

(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

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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