19-40757355-A-G
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4BP6_Moderate
The NM_004596.5(SNRPA):c.97A>G(p.Ile33Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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 Likely benign (★).
Frequency
Consequence
NM_004596.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Spliceosomepathy Benign:1
Splicing-related gene mutations might affect in different ways the expression of a single gene or multiple genes. Exome sequencing analyses by Variant Interpreter identified, in independent assays of the patients, three homozygous missense variants in exon 2 of SNRPA (hg19; chr19:41,263,260, chr19:41,263,261, and chr19:41,263,263; NM_004596.4). These variants were described as c.97A>G, c.98T>C, and c.100T>A and cause a change in two contiguous amino acids: p.Ile33Ala and p.Phe34Ile. The in-silico analyses (CFSSP, ExPASy web tool) showed a gained rich-α-helix region. Six different bioinformatic platforms predicted a pathogenic consequence for p.Ile33Ala and p.Phe34Ile; however, a more pathogenic score (-8.53, PROVEAN web tool) was predicted when both mutations were analyzed combined. SNRPA encodes for a protein that associates with the stem loop II of the U1 RNA. SNRPA/U1-A along with SNRNP70/U1-70K, SNRPC/U1-C and a core of proteins known as Sm, conform the U1 small nuclear ribonucleoprotein complex. The PD/ID and growth, eye, craniofacial and hand anomalies in our patients, are features also seen in other spliceosomepathies. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at