rs58263806

Variant names:

• chr1-92833636-G-A
• rs58263806
• NM_000969.5:c.165G>A
• RPL5 p.Val55Val

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000969.5(RPL5):​c.165G>A​(p.Val55Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00401 in 1,611,662 control chromosomes in the GnomAD database, including 210 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (120 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (90 hom.)
• Consequence: RPL5 NM_000969.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.166
• Publications: 3 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 1-92833636-G-A is Benign according to our data. Variant chr1-92833636-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 238196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.166 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0699 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000969.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL5	NM_000969.5	MANE Select	c.165G>A	p.Val55Val	synonymous	Exon 3 of 8	NP_000960.2
	DIPK1A	NM_001252273.2		c.475-602C>T		intron	N/A	NP_001239202.1	Q5T7M9-2
	RPL5	NR_146333.1		n.294G>A		non_coding_transcript_exon	Exon 3 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL5	ENST00000370321.8	TSL:1 MANE Select	c.165G>A	p.Val55Val	synonymous	Exon 3 of 8	ENSP00000359345.2	P46777
	DIPK1A	ENST00000615519.4	TSL:1	c.475-602C>T		intron	N/A	ENSP00000483279.1	Q5T7M9-2
	RPL5	ENST00000880515.1		c.165G>A	p.Val55Val	synonymous	Exon 3 of 8	ENSP00000550574.1

Frequencies

GnomAD3 genomes AF: 0.0208 AC: 3170 AN: 152138 Hom.: 118 Cov.: 32

Gnomad AFR AF: 0.0719

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00825

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0196

GnomAD2 exomes AF: 0.00574 AC: 1443 AN: 251208 AF XY: 0.00417

Gnomad AFR exome AF: 0.0762

Gnomad AMR exome AF: 0.00428

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000238

Gnomad OTH exome AF: 0.00359

GnomAD4 exome AF: 0.00224 AC: 3274 AN: 1459406 Hom.: 90 Cov.: 30 AF XY: 0.00187 AC XY: 1356 AN XY: 726034

African (AFR) AF: 0.0758 AC: 2532 AN: 33390

American (AMR) AF: 0.00452 AC: 202 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.000383 AC: 10 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.000151 AC: 13 AN: 86158

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53320

Middle Eastern (MID) AF: 0.00402 AC: 17 AN: 4228

European-Non Finnish (NFE) AF: 0.000181 AC: 201 AN: 1111552

Other (OTH) AF: 0.00496 AC: 299 AN: 60222

GnomAD4 genome AF: 0.0209 AC: 3184 AN: 152256 Hom.: 120 Cov.: 32 AF XY: 0.0206 AC XY: 1532 AN XY: 74442

African (AFR) AF: 0.0720 AC: 2992 AN: 41534

American (AMR) AF: 0.00824 AC: 126 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 68022

Other (OTH) AF: 0.0194 AC: 41 AN: 2114

Alfa AF: 0.00938 Hom.: 29

Bravo AF: 0.0236

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000652

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Diamond-Blackfan anemia (2)
-	-	2	Diamond-Blackfan anemia 6 (2)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	6.3
DANN	Benign	0.85
PhyloP100		0.17
Mutation Taster		=99/1	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs58263806;

hg19: chr1-93299193;