1-1312247-C-T

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

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.51
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 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
INTS11NM_017871.6 linkuse as main transcriptc.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
INTS11ENST00000435064.6 linkuse as main transcriptc.1586G>A p.Arg529His missense_variant 15/171 NM_017871.6 ENSP00000413493 P1Q5TA45-1

Frequencies

GnomAD3 genomes
AF:
0.0000482
AC:
7
AN:
145228
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000747
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000718
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000213
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000150
Gnomad OTH
AF:
0.000504
GnomAD3 exomes
AF:
0.0000332
AC:
5
AN:
150644
Hom.:
0
AF XY:
0.0000374
AC XY:
3
AN XY:
80258
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000405
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000179
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000295
AC:
41
AN:
1387688
Hom.:
0
Cov.:
36
AF XY:
0.0000293
AC XY:
20
AN XY:
682604
show subpopulations
Gnomad4 AFR exome
AF:
0.000188
Gnomad4 AMR exome
AF:
0.0000561
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000101
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000224
Gnomad4 OTH exome
AF:
0.0000174
GnomAD4 genome
AF:
0.0000482
AC:
7
AN:
145228
Hom.:
0
Cov.:
33
AF XY:
0.0000432
AC XY:
3
AN XY:
69440
show subpopulations
Gnomad4 AFR
AF:
0.0000747
Gnomad4 AMR
AF:
0.0000718
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000213
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000150
Gnomad4 OTH
AF:
0.000504
Alfa
AF:
0.0000581
Hom.:
0
Bravo
AF:
0.0000529
ExAC
AF:
0.0000435
AC:
4

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 submitterclinical testingAmbry GeneticsMay 24, 2023The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.032
.;.;.;T;T;T;.;.;.
Eigen
Benign
0.035
Eigen_PC
Benign
-0.059
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.97
D;D;D;D;D;D;D;D;D
M_CAP
Benign
0.041
D
MetaRNN
Benign
0.40
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
1.3
.;.;.;.;L;.;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-1.8
N;N;.;.;N;N;.;N;N
REVEL
Benign
0.17
Sift
Uncertain
0.020
D;D;.;.;D;D;.;D;D
Sift4G
Benign
0.084
T;T;T;T;T;T;T;T;T
Polyphen
0.97, 0.99, 0.99, 0.98
.;.;.;.;D;D;.;D;D
Vest4
0.49
MutPred
0.49
.;.;.;.;Gain of loop (P = 0.0435);.;.;.;.;
MVP
0.60
MPC
0.035
ClinPred
0.39
T
GERP RS
3.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.44
gMVP
0.45

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: rs759845797; hg19: chr1-1247627; API