1-92837894-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000969.5(RPL5):c.705+261G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.888 in 479,690 control chromosomes in the GnomAD database, including 190,044 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.86 (56513 hom., cov: 33)
  • Exomes 𝑓: 0.90 (133531 hom.)
• Consequence: RPL5 NM_000969.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPL5	NM_000969.5	c.705+261G>T		intron_variant		ENST00000370321.8
DIPK1A	NM_001252273.2	c.475-4860C>A		intron_variant
RPL5	NR_146333.1	n.764+261G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPL5	ENST00000370321.8	c.705+261G>T		intron_variant		1	NM_000969.5	P1

Frequencies

GnomAD3 genomes AF: 0.858 AC: 130578 AN: 152128 Hom.: 56495 Cov.: 33

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.955

Gnomad AMR AF: 0.897

Gnomad ASJ AF: 0.954

Gnomad EAS AF: 0.962

Gnomad SAS AF: 0.944

Gnomad FIN AF: 0.883

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.894

Gnomad OTH AF: 0.853

GnomAD4 exome AF: 0.902 AC: 295446 AN: 327442 Hom.: 133531 AF XY: 0.907 AC XY: 159264 AN XY: 175690

Gnomad4 AFR exome AF: 0.751

Gnomad4 AMR exome AF: 0.917

Gnomad4 ASJ exome AF: 0.945

Gnomad4 EAS exome AF: 0.967

Gnomad4 SAS exome AF: 0.945

Gnomad4 FIN exome AF: 0.882

Gnomad4 NFE exome AF: 0.893

Gnomad4 OTH exome AF: 0.892

GnomAD4 genome AF: 0.858 AC: 130651 AN: 152248 Hom.: 56513 Cov.: 33 AF XY: 0.861 AC XY: 64069 AN XY: 74434

Gnomad4 AFR AF: 0.746

Gnomad4 AMR AF: 0.898

Gnomad4 ASJ AF: 0.954

Gnomad4 EAS AF: 0.962

Gnomad4 SAS AF: 0.943

Gnomad4 FIN AF: 0.883

Gnomad4 NFE AF: 0.894

Gnomad4 OTH AF: 0.853

Alfa AF: 0.851 Hom.: 7867

Bravo AF: 0.852

Asia WGS AF: 0.908 AC: 3159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	5.9
Dann	Benign	0.45

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

LitVar

Other links and lift over

dbSNP: rs6659942; hg19: chr1-93303451;