dbSNP rs938367538: RPL5:p.Asp234Asn (chr1-92837628-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_000969.5(RPL5):c.700G>A(p.Asp234Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D234G) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

RPL5
NM_000969.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.73

Variant links:

Genes affected

RPL5 (HGNC:10360): (ribosomal protein L5) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of four RNA species and approximately 80 structurally distinct proteins. This gene encodes a member of the L18P family of ribosomal proteins and component of the 60S subunit. The encoded protein binds 5S rRNA to form a stable complex called the 5S ribonucleoprotein particle (RNP), which is necessary for the transport of nonribosome-associated cytoplasmic 5S rRNA to the nucleolus for assembly into ribosomes. The encoded protein may also function to inhibit tumorigenesis through the activation of downstream tumor suppressors and the downregulation of oncoprotein expression. Mutations in this gene have been identified in patients with Diamond-Blackfan Anemia (DBA). This gene is co-transcribed with the small nucleolar RNA gene U21, which is located in its fifth intron. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed throughout the genome. [provided by RefSeq, Mar 2017]

RPL5 links:

DIPK1A (HGNC:32213): (divergent protein kinase domain 1A) This gene encodes a member of the FAM69 family of cysteine-rich type II transmembrane proteins. These proteins localize to the endoplasmic reticulum but their specific functions are unknown. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

DIPK1A links:

SNORD21 (HGNC:10144): (small nucleolar RNA, C/D box 21) This gene encodes a small nucleolar RNA (snoRNA) that may be involved in biogenesis of the large (28S) ribosomal subunit. This gene is found within an intron of the RPL5 gene. [provided by RefSeq, Mar 2009]

SNORD21 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35261464).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPL5	NM_000969.5 link	c.700G>A	p.Asp234Asn	missense_variant	Exon 6 of 8	ENST00000370321.8	NP_000960.2	P46777A2RUM7
DIPK1A	NM_001252273.2 link	c.475-4594C>T		intron_variant	Intron 4 of 4		NP_001239202.1	Q5T7M9-2
RPL5	NR_146333.1 link	n.759G>A		non_coding_transcript_exon_variant	Exon 6 of 8
SNORD21	NR_000006.8 link	n.*245G>A		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPL5	ENST00000370321.8 link	c.700G>A	p.Asp234Asn	missense_variant	Exon 6 of 8	1	NM_000969.5	ENSP00000359345.2		P46777

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459578

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726128

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Benign

-0.070

BayesDel_noAF

Benign

-0.34

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

T;.;T

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.85

.;D;D

M_CAP

Benign

0.019

MetaRNN

Benign

0.35

T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.7

M;.;M

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.8

.;.;D

REVEL

Benign

0.20

Sift

Benign

0.042

.;.;D

Sift4G

Benign

0.12

.;.;T

Polyphen

0.14

B;.;B

Vest4

0.54

MutPred

0.36

Gain of MoRF binding (P = 0.0357);.;Gain of MoRF binding (P = 0.0357);

MVP

0.68

MPC

1.4

ClinPred

0.98

GERP RS

5.1

Varity_R

0.66

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over