9-124857964-C-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_007209.4(RPL35):c.326G>A(p.Arg109Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000403 in 1,612,270 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R109L) has been classified as Uncertain significance.
Frequency
Consequence
NM_007209.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPL35 | NM_007209.4 | c.326G>A | p.Arg109Gln | missense_variant | 4/4 | ENST00000348462.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPL35 | ENST00000348462.6 | c.326G>A | p.Arg109Gln | missense_variant | 4/4 | 1 | NM_007209.4 | P1 | |
RPL35 | ENST00000487431.1 | n.704G>A | non_coding_transcript_exon_variant | 3/3 | 1 | ||||
RPL35 | ENST00000373570.8 | c.*115G>A | 3_prime_UTR_variant | 5/5 | 3 | ||||
RPL35 | ENST00000493018.5 | c.*297G>A | 3_prime_UTR_variant, NMD_transcript_variant | 5/5 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152262Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251230Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135848
GnomAD4 exome AF: 0.0000411 AC: 60AN: 1459890Hom.: 0 Cov.: 34 AF XY: 0.0000275 AC XY: 20AN XY: 726256
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152380Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74518
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 03, 2023 | Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals affected with RPL35-related conditions. This variant is present in population databases (rs28620639, gnomAD 0.02%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 109 of the RPL35 protein (p.Arg109Gln). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at