Variant rs2306852 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000261191.12(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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0051 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0066 ( 54 hom. )

Consequence

INTS13
ENST00000261191.12 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.87

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 made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
INTS13	NM_018164.3 linkuse as main transcript	c.197T>C	p.Met66Thr	missense_variant	2/17	ENST00000261191.12	NP_060634.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INTS13	ENST00000261191.12 linkuse as main transcript	c.197T>C	p.Met66Thr	missense_variant	2/17	1	NM_018164.3	ENSP00000261191	P1	Q9NVM9-1
INTS13	ENST00000544548.5 linkuse as main transcript	c.197T>C	p.Met66Thr	missense_variant	3/7	3		ENSP00000446183
INTS13	ENST00000537336.1 linkuse as main transcript	c.197T>C	p.Met66Thr	missense_variant	2/4	3		ENSP00000443066
INTS13	ENST00000538727.5 linkuse as main transcript	c.-4+1189T>C		intron_variant		4		ENSP00000448467

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

GnomAD3 exomes

AF:

0.00706

AC:

1775

AN:

251278

Hom.:

AF XY:

0.00756

AC XY:

1027

AN XY:

135814

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 SAS exome

AF:

0.0121

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

Gnomad4 AFR exome

AF:

0.000957

Gnomad4 AMR exome

AF:

0.00333

Gnomad4 ASJ exome

AF:

0.00819

Gnomad4 EAS exome

AF:

0.00592

Gnomad4 SAS exome

AF:

0.0116

Gnomad4 FIN exome

AF:

0.0129

Gnomad4 NFE exome

AF:

0.00624

Gnomad4 OTH exome

AF:

0.00583

GnomAD4 genome

AF:

0.00511

AC:

779

AN:

152326

Hom.:

Cov.:

AF XY:

0.00580

AC XY:

432

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000914

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.00864

Gnomad4 EAS

AF:

0.00386

Gnomad4 SAS

AF:

0.0166

Gnomad4 FIN

AF:

0.0135

Gnomad4 NFE

AF:

0.00620

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00617

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

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

MutationTaster

Benign

1.0

D;D

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

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over