rs116874993
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_000996.4(RPL35A):c.*6C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000254 in 1,600,170 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00026 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00025 ( 2 hom. )
Consequence
RPL35A
NM_000996.4 3_prime_UTR
NM_000996.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.35
Genes affected
RPL35A (HGNC:10345): (ribosomal protein L35a) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L35AE family of ribosomal proteins. It is located in the cytoplasm. The rat protein has been shown to bind to both initiator and elongator tRNAs, and thus, it is located at the P site, or P and A sites, of the ribosome. Although this gene was originally mapped to chromosome 18, it has been established that it is located at 3q29-qter. Alternative splicing results in multiple transcript variants. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Oct 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
?
Variant 3-197955779-C-T is Benign according to our data. Variant chr3-197955779-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 344530.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High AC in GnomAd4 at 39 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPL35A | NM_000996.4 | c.*6C>T | 3_prime_UTR_variant | 5/5 | ENST00000647248.2 | ||
IQCG | NM_032263.5 | c.-60+3750G>A | intron_variant | ENST00000265239.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPL35A | ENST00000647248.2 | c.*6C>T | 3_prime_UTR_variant | 5/5 | NM_000996.4 | P1 | |||
IQCG | ENST00000265239.11 | c.-60+3750G>A | intron_variant | 1 | NM_032263.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000257 AC: 39AN: 151970Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000414 AC: 104AN: 251306Hom.: 1 AF XY: 0.000375 AC XY: 51AN XY: 135840
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GnomAD4 exome AF: 0.000254 AC: 368AN: 1448082Hom.: 2 Cov.: 27 AF XY: 0.000236 AC XY: 170AN XY: 721142
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GnomAD4 genome ? AF: 0.000256 AC: 39AN: 152088Hom.: 1 Cov.: 32 AF XY: 0.000350 AC XY: 26AN XY: 74348
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 07, 2017 | - - |
Diamond-Blackfan anemia 5 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
RPL35A-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 09, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at