Variant 1-1312250-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017871.6(INTS11):c.1583T>C(p.Leu528Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000843 in 1,541,402 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

INTS11
NM_017871.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.31

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.021386743).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INTS11	NM_017871.6 linkuse as main transcript	c.1583T>C	p.Leu528Ser	missense_variant	15/17	ENST00000435064.6	NP_060341.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INTS11	ENST00000435064.6 linkuse as main transcript	c.1583T>C	p.Leu528Ser	missense_variant	15/17	1	NM_017871.6	ENSP00000413493	P1	Q5TA45-1

Frequencies

GnomAD3 genomes

AF:

0.000515

AC:

AN:

149472

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00183

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000675

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000989

AC:

AN:

151684

Hom.:

AF XY:

0.0000620

AC XY:

AN XY:

80618

show subpopulations

Gnomad AFR exome

AF:

0.00160

Gnomad AMR exome

AF:

0.0000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.0000381

AC:

AN:

1391818

Hom.:

Cov.:

AF XY:

0.0000263

AC XY:

AN XY:

685272

show subpopulations

Gnomad4 AFR exome

AF:

0.00153

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000521

GnomAD4 genome

AF:

0.000515

AC:

AN:

149584

Hom.:

Cov.:

AF XY:

0.000523

AC XY:

AN XY:

72652

show subpopulations

Gnomad4 AFR

AF:

0.00183

Gnomad4 AMR

AF:

0.0000674

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000404

Hom.:

ESP6500AA

AF:

0.00240

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000434

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 08, 2024

The c.1583T>C (p.L528S) alteration is located in exon 15 (coding exon 15) of the CPSF3L gene. This alteration results from a T to C substitution at nucleotide position 1583, causing the leucine (L) at amino acid position 528 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.57

CADD

Benign

5.6

DANN

Benign

0.55

DEOGEN2

Benign

0.0031

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

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.73

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

M_CAP

Benign

0.015

MetaRNN

Benign

0.021

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

.;.;.;.;L;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

0.33

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

REVEL

Benign

0.064

Sift

Benign

0.48

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

Sift4G

Benign

0.83

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

Polyphen

0.0, 0.0010

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

Vest4

0.35

MVP

0.49

MPC

0.037

ClinPred

0.0063

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.065

gMVP

0.29

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