Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_033547.4(INTS4):c.2411G>A(p.Arg804Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000391 in 1,611,876 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 (★).
INTS4 (HGNC:25048): (integrator complex subunit 4) INTS4 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]
AAMDC (HGNC:30205): (adipogenesis associated Mth938 domain containing) Predicted to be involved in positive regulation of fat cell differentiation. Predicted to act upstream of or within negative regulation of apoptotic process and positive regulation of transcription by RNA polymerase II. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]
Review Status: criteria provided, single submitter
Collection Method: clinical testing
The c.2411G>A (p.R804Q) alteration is located in exon 20 (coding exon 20) of the INTS4 gene. This alteration results from a G to A substitution at nucleotide position 2411, causing the arginine (R) at amino acid position 804 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -