rs145244860
Positions:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM1BP4_StrongBP6_Very_StrongBS2
The NM_000996.4(RPL35A):c.266G>A(p.Arg89Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000345 in 1,614,172 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.0019 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00019 ( 0 hom. )
Consequence
RPL35A
NM_000996.4 missense
NM_000996.4 missense
Scores
3
15
Clinical Significance
Conservation
PhyloP100: 8.03
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 -14 ACMG points.
PM1
?
In a chain 60S ribosomal protein L35a (size 109) in uniprot entity RL35A_HUMAN there are 6 pathogenic changes around while only 2 benign (75%) in NM_000996.4
BP4
?
Computational evidence support a benign effect (MetaRNN=0.010737509).
BP6
?
Variant 3-197954104-G-A is Benign according to our data. Variant chr3-197954104-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 344529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High AC in GnomAd4 at 282 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPL35A | NM_000996.4 | c.266G>A | p.Arg89Gln | missense_variant | 4/5 | ENST00000647248.2 | |
IQCG | NM_032263.5 | c.-60+5425C>T | intron_variant | ENST00000265239.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPL35A | ENST00000647248.2 | c.266G>A | p.Arg89Gln | missense_variant | 4/5 | NM_000996.4 | P1 | ||
IQCG | ENST00000265239.11 | c.-60+5425C>T | intron_variant | 1 | NM_032263.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00186 AC: 283AN: 152170Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000497 AC: 125AN: 251406Hom.: 0 AF XY: 0.000412 AC XY: 56AN XY: 135890
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GnomAD4 exome AF: 0.000188 AC: 275AN: 1461884Hom.: 0 Cov.: 31 AF XY: 0.000165 AC XY: 120AN XY: 727240
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GnomAD4 genome ? AF: 0.00185 AC: 282AN: 152288Hom.: 0 Cov.: 32 AF XY: 0.00187 AC XY: 139AN XY: 74464
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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
Diamond-Blackfan anemia 5 Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 15, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.;N
REVEL
Benign
Sift
Benign
T;T;.;T
Sift4G
Benign
T;T;.;T
Polyphen
B;B;B;.
Vest4
MVP
MPC
ClinPred
T
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gMVP
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