Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005839.4(SRRM1):c.775C>A(p.Pro259Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,455,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
SRRM1 (HGNC:16638): (serine and arginine repetitive matrix 1) Enables RNA binding activity. Predicted to be involved in mRNA splicing, via spliceosome. Located in nuclear speck. Part of catalytic step 2 spliceosome. Biomarker of gestational diabetes. [provided by Alliance of Genome Resources, Apr 2022]
Review Status: criteria provided, single submitter
Collection Method: clinical testing
The c.775C>A (p.P259T) alteration is located in exon 7 (coding exon 7) of the SRRM1 gene. This alteration results from a C to A substitution at nucleotide position 775, causing the proline (P) at amino acid position 259 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -