rs747481892

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PM5BP4

The NM_017871.6(INTS11):ā€‹c.1543G>Cā€‹(p.Val515Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000194 in 1,549,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V515M) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

INTS11
NM_017871.6 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.36
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr1-1312290-C-T is described in Lovd as [Likely_pathogenic].
BP4
Computational evidence support a benign effect (MetaRNN=0.34633443).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
INTS11NM_017871.6 linkc.1543G>C p.Val515Leu 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
INTS11ENST00000435064.6 linkc.1543G>C p.Val515Leu missense_variant Exon 15 of 17 1 NM_017871.6 ENSP00000413493.2 Q5TA45-1

Frequencies

GnomAD3 genomes
AF:
0.00000664
AC:
1
AN:
150644
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000243
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000143
AC:
2
AN:
1398382
Hom.:
0
Cov.:
36
AF XY:
0.00000145
AC XY:
1
AN XY:
689808
show subpopulations
Gnomad4 AFR exome
AF:
0.0000314
Gnomad4 AMR exome
AF:
0.00
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:
9.27e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000664
AC:
1
AN:
150644
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
73236
show subpopulations
Gnomad4 AFR
AF:
0.0000243
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.24
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.025
.;.;.;T;T;T;.;.;.
Eigen
Benign
-0.12
Eigen_PC
Benign
0.043
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.93
D;D;D;D;D;D;D;D;D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.35
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.99
.;.;.;.;L;.;.;.;.
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
-1.2
N;N;.;.;N;N;.;N;N
REVEL
Benign
0.093
Sift
Benign
0.074
T;T;.;.;T;T;.;T;T
Sift4G
Benign
0.20
T;T;T;T;T;T;T;T;T
Polyphen
0.0060, 0.012, 0.021, 0.010
.;.;.;.;B;B;.;B;B
Vest4
0.48
MutPred
0.49
.;.;.;.;Gain of helix (P = 0.132);.;.;.;.;
MVP
0.57
MPC
0.032
ClinPred
0.66
D
GERP RS
4.5
Varity_R
0.42
gMVP
0.48

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.

Other links and lift over

dbSNP: rs747481892; hg19: chr1-1247670; API