NM_000969.5:c.-58G>T

Variant names:

• chr1-92832057-G-T
• rs200437092
• NM_000969.5:c.-58G>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_000969.5(RPL5):​c.-58G>T variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.00193 in 1,611,648 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0015 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0020 (10 hom.)
• Consequence: RPL5 NM_000969.5 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.86
• Publications: 0 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]

RPL5 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia 6

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• Diamond-Blackfan anemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 1-92832057-G-T is Benign according to our data. Variant chr1-92832057-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 298198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 231 AD gene.

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.-58G>T		5_prime_UTR	Exon 1 of 8	NP_000960.2
	RPL5	NR_146333.1		n.72G>T		non_coding_transcript_exon	Exon 1 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL5	ENST00000370321.8	TSL:1 MANE Select	c.-58G>T		5_prime_UTR	Exon 1 of 8	ENSP00000359345.2
	RPL5	ENST00000880515.1		c.-58G>T		5_prime_UTR	Exon 1 of 8	ENSP00000550574.1
	RPL5	ENST00000880516.1		c.-58G>T		5_prime_UTR	Exon 1 of 8	ENSP00000550575.1

Frequencies

GnomAD3 genomes AF: 0.00151 AC: 230 AN: 152234 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00244

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.00197 AC: 2873 AN: 1459296 Hom.: 10 Cov.: 31 AF XY: 0.00198 AC XY: 1434 AN XY: 725772

African (AFR) AF: 0.000269 AC: 9 AN: 33434

American (AMR) AF: 0.000428 AC: 19 AN: 44358

Ashkenazi Jewish (ASJ) AF: 0.00542 AC: 141 AN: 26026

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39622

South Asian (SAS) AF: 0.00136 AC: 117 AN: 85816

European-Finnish (FIN) AF: 0.00119 AC: 63 AN: 52920

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.00218 AC: 2417 AN: 1111070

Other (OTH) AF: 0.00174 AC: 105 AN: 60284

GnomAD4 genome AF: 0.00152 AC: 231 AN: 152352 Hom.: 1 Cov.: 33 AF XY: 0.00145 AC XY: 108 AN XY: 74508

African (AFR) AF: 0.000192 AC: 8 AN: 41590

American (AMR) AF: 0.000261 AC: 4 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00749 AC: 26 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00290 AC: 14 AN: 4834

European-Finnish (FIN) AF: 0.000753 AC: 8 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00244 AC: 166 AN: 68026

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00148 Hom.: 0

Bravo AF: 0.00127

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	16
DANN	Benign	0.85
PhyloP100		3.9
PromoterAI		0.018	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=291/9	polymorphism

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

Other links and lift over

dbSNP: rs200437092; hg19: chr1-93297614;