4-105682939-G-C
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_020395.4(INTS12):āc.1183C>Gā(p.Pro395Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,613,922 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 (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.0000014 ( 0 hom. )
Consequence
INTS12
NM_020395.4 missense
NM_020395.4 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 4.82
Genes affected
INTS12 (HGNC:25067): (integrator complex subunit 12) INTS12 is a subunit of the Integrator complex, which associates with the C-terminal domain of RNA polymerase II large subunit (POLR2A; MIM 180660) and mediates 3-prime end processing of small nuclear RNAs U1 (RNU1; MIM 180680) and U2 (RNU2; MIM 180690) (Baillat et al., 2005 [PubMed 16239144]).[supplied by OMIM, Mar 2008]
ARHGEF38 (HGNC:25968): (Rho guanine nucleotide exchange factor 38) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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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=0.11655754).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INTS12 | NM_020395.4 | c.1183C>G | p.Pro395Ala | missense_variant | 8/8 | ENST00000340139.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INTS12 | ENST00000340139.10 | c.1183C>G | p.Pro395Ala | missense_variant | 8/8 | 1 | NM_020395.4 | P1 | |
INTS12 | ENST00000451321.6 | c.1183C>G | p.Pro395Ala | missense_variant | 7/7 | 1 | P1 | ||
INTS12 | ENST00000394735.5 | c.1183C>G | p.Pro395Ala | missense_variant | 8/8 | 5 | P1 | ||
ARHGEF38 | ENST00000503289.1 | n.325G>C | non_coding_transcript_exon_variant | 4/5 | 3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152104Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251408Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135874
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461818Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727208
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152104Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74320
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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 04, 2023 | The c.1183C>G (p.P395A) alteration is located in exon 8 (coding exon 6) of the INTS12 gene. This alteration results from a C to G substitution at nucleotide position 1183, causing the proline (P) at amino acid position 395 to be replaced by an alanine (A). 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;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
.;.;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;.
REVEL
Benign
Sift
Uncertain
D;D;D;.
Sift4G
Benign
T;T;T;T
Polyphen
B;B;B;.
Vest4
MutPred
Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);
MVP
MPC
0.87
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