1-1312056-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017871.6(INTS11):​c.1699C>T​(p.Pro567Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)

Consequence

INTS11
NM_017871.6 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.67
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21092352).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
INTS11NM_017871.6 linkc.1699C>T p.Pro567Ser missense_variant Exon 16 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.1699C>T p.Pro567Ser missense_variant Exon 16 of 17 1 NM_017871.6 ENSP00000413493.2 Q5TA45-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 15, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1699C>T (p.P567S) alteration is located in exon 16 (coding exon 16) of the CPSF3L gene. This alteration results from a C to T substitution at nucleotide position 1699, causing the proline (P) at amino acid position 567 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
0.068
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0042
.;.;.;T;T;T;.;.;.
Eigen
Benign
-0.16
Eigen_PC
Benign
-0.056
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.93
D;D;D;D;D;D;D;D;D
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.21
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.34
.;.;.;.;N;.;.;.;.
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-0.26
N;N;.;.;N;N;.;N;N
REVEL
Benign
0.10
Sift
Benign
0.079
T;T;.;.;T;T;.;T;T
Sift4G
Benign
0.54
T;T;T;T;T;T;T;T;T
Polyphen
0.0, 0.0010
.;.;.;.;B;B;.;B;B
Vest4
0.21
MutPred
0.32
.;.;.;.;Loss of sheet (P = 0.0126);.;.;.;.;
MVP
0.66
MPC
0.031
ClinPred
0.47
T
GERP RS
4.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.17
gMVP
0.17

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-1247436; API