Variant NM_017871.6:c.1577C>T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_017871.6(INTS11):c.1577C>T(p.Thr526Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000923 in 1,539,258 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000086 ( 2 hom. )

Consequence

INTS11
NM_017871.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.24

Variant links:

Genes affected

INTS11 (HGNC:26052): (integrator complex subunit 11) The Integrator complex contains at least 12 subunits and associates with the C-terminal domain of RNA polymerase II large subunit (POLR2A; MIM 180660) and mediates the 3-prime end processing of small nuclear RNAs U1 (RNU1; MIM 180680) and U2 (RNU2; MIM 180690). INTS11, or CPSF3L, is the catalytic subunit of the Integrator complex (Baillat et al., 2005 [PubMed 16239144]).[supplied by OMIM, Mar 2008]

INTS11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04305938).

BP6

Variant 1-1312256-G-A is Benign according to our data. Variant chr1-1312256-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3529416.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INTS11	NM_017871.6 link	c.1577C>T	p.Thr526Met	missense_variant	Exon 15 of 17	ENST00000435064.6	NP_060341.2	Q5TA45-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INTS11	ENST00000435064.6 link	c.1577C>T	p.Thr526Met	missense_variant	Exon 15 of 17	1	NM_017871.6	ENSP00000413493.2		Q5TA45-1

Frequencies

GnomAD3 genomes

AF:

0.000150

AC:

AN:

146216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000124

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00150

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000300

Gnomad OTH

AF:

0.000502

GnomAD3 exomes

AF:

0.000144

AC:

AN:

152530

Hom.:

AF XY:

0.000161

AC XY:

AN XY:

80928

show subpopulations

Gnomad AFR exome

AF:

0.000114

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000263

Gnomad FIN exome

AF:

0.000875

Gnomad NFE exome

AF:

0.0000175

Gnomad OTH exome

AF:

0.000231

GnomAD4 exome

AF:

0.0000861

AC:

120

AN:

1392922

Hom.:

Cov.:

AF XY:

0.0000845

AC XY:

AN XY:

686296

show subpopulations

Gnomad4 AFR exome

AF:

0.000157

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000553

Gnomad4 SAS exome

AF:

0.000328

Gnomad4 FIN exome

AF:

0.00112

Gnomad4 NFE exome

AF:

0.0000260

Gnomad4 OTH exome

AF:

0.0000520

GnomAD4 genome

AF:

0.000150

AC:

AN:

146336

Hom.:

Cov.:

AF XY:

0.000213

AC XY:

AN XY:

70314

show subpopulations

Gnomad4 AFR

AF:

0.000123

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00150

Gnomad4 NFE

AF:

0.0000300

Gnomad4 OTH

AF:

0.000496

Alfa

AF:

0.000123

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000860

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Dec 03, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.48

CADD

Benign

8.8

DANN

Benign

0.88

DEOGEN2

Benign

0.031

.;.;.;T;T;T;.;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.81

T;T;T;T;T;T;T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.043

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

.;.;.;.;M;.;.;.;.

PrimateAI

Benign

0.41

PROVEAN

Benign

-2.3

N;N;.;.;N;N;.;N;N

REVEL

Benign

0.091

Sift

Benign

0.13

T;T;.;.;T;T;.;T;T

Sift4G

Benign

0.088

T;T;D;T;T;D;T;T;T

Polyphen

0.0030, 0.058, 0.029, 0.020

.;.;.;.;B;B;.;B;B

Vest4

0.31

MutPred

0.35

.;.;.;.;Loss of helix (P = 0.0376);.;.;.;.;

MVP

0.38

MPC

0.036

ClinPred

0.022

GERP RS

-1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.054

gMVP

0.44

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over