1-1312247-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_017871.6(INTS11):c.1586G>A(p.Arg529His) variant causes a missense change. The variant allele was found at a frequency of 0.0000313 in 1,532,916 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. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000048 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000030 ( 0 hom. )
Consequence
INTS11
NM_017871.6 missense
NM_017871.6 missense
Scores
1
4
14
Clinical Significance
Conservation
PhyloP100: 5.51
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.39997056).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
INTS11 | NM_017871.6 | c.1586G>A | p.Arg529His | 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 | c.1586G>A | p.Arg529His | missense_variant | 15/17 | 1 | NM_017871.6 | ENSP00000413493 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000482 AC: 7AN: 145228Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000332 AC: 5AN: 150644Hom.: 0 AF XY: 0.0000374 AC XY: 3AN XY: 80258
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GnomAD4 exome AF: 0.0000295 AC: 41AN: 1387688Hom.: 0 Cov.: 36 AF XY: 0.0000293 AC XY: 20AN XY: 682604
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GnomAD4 genome AF: 0.0000482 AC: 7AN: 145228Hom.: 0 Cov.: 33 AF XY: 0.0000432 AC XY: 3AN XY: 69440
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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 | May 24, 2023 | The c.1586G>A (p.R529H) alteration is located in exon 15 (coding exon 15) of the CPSF3L gene. This alteration results from a G to A substitution at nucleotide position 1586, causing the arginine (R) at amino acid position 529 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;.;.;T;T;T;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;.;.;L;.;.;.;.
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.;.;N;N;.;N;N
REVEL
Benign
Sift
Uncertain
D;D;.;.;D;D;.;D;D
Sift4G
Benign
T;T;T;T;T;T;T;T;T
Polyphen
0.97, 0.99, 0.99, 0.98
.;.;.;.;D;D;.;D;D
Vest4
MutPred
0.49
.;.;.;.;Gain of loop (P = 0.0435);.;.;.;.;
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at