4-105695520-T-A
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_020395.4(INTS12):c.305A>T(p.Asp102Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000157 in 1,592,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000015 ( 0 hom. )
Consequence
INTS12
NM_020395.4 missense
NM_020395.4 missense
Scores
1
6
12
Clinical Significance
Conservation
PhyloP100: 5.92
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 Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.22343552).
BS2
High AC in GnomAdExome4 at 22 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INTS12 | NM_020395.4 | c.305A>T | p.Asp102Val | missense_variant | 4/8 | ENST00000340139.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INTS12 | ENST00000340139.10 | c.305A>T | p.Asp102Val | missense_variant | 4/8 | 1 | NM_020395.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152230Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000299 AC: 7AN: 234270Hom.: 0 AF XY: 0.0000395 AC XY: 5AN XY: 126610
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GnomAD4 exome AF: 0.0000153 AC: 22AN: 1440614Hom.: 0 Cov.: 29 AF XY: 0.0000140 AC XY: 10AN XY: 716030
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152230Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74370
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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 | Oct 12, 2022 | The c.305A>T (p.D102V) alteration is located in exon 4 (coding exon 2) of the INTS12 gene. This alteration results from a A to T substitution at nucleotide position 305, causing the aspartic acid (D) at amino acid position 102 to be replaced by a valine (V). 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
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;.;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L;.;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;.;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;.;D;D
Sift4G
Uncertain
D;D;D;D;.;.
Polyphen
B;B;B;.;.;.
Vest4
MVP
MPC
0.46
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
DS_DG_spliceai
Position offset: 32
Find out detailed SpliceAI scores and Pangolin per-transcript scores at