16-89561052-T-G

Variant names:

• chr16-89561052-T-G
• rs2280370
• NM_000977.4:c.93T>G

Variant summary

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

The NM_000977.4(RPL13):​c.93T>G​(p.Arg31Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,605,014 control chromosomes in the GnomAD database, including 30,603 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3467 hom., cov: 34)
  • Exomes 𝑓: 0.19 (27136 hom.)
• Consequence: RPL13 NM_000977.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.289
• Publications: 24 publications found

Genes affected

RPL13 (HGNC:10303): (ribosomal protein L13) 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 L13E family of ribosomal proteins. It is located in the cytoplasm. This gene is expressed at significantly higher levels in benign breast lesions than in breast carcinomas. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2011]

RPL13 Gene-Disease associations (from GenCC):

• spondyloepimetaphyseal dysplasia, Isidor-Toutain type

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)
• spondyloepiphyseal dysplasia

  Inheritance: AD Classification: MODERATE Submitted by: Franklin by Genoox

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 16-89561052-T-G is Benign according to our data. Variant chr16-89561052-T-G is described in ClinVar as Benign. ClinVar VariationId is 1327970.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.289 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000977.4. 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
	RPL13	NM_000977.4	MANE Select	c.93T>G	p.Arg31Arg	synonymous	Exon 2 of 6	NP_000968.2
	RPL13	NM_033251.2		c.93T>G	p.Arg31Arg	synonymous	Exon 1 of 5	NP_150254.1	P26373-1
	RPL13	NM_001243131.1		c.93T>G	p.Arg31Arg	synonymous	Exon 2 of 7	NP_001230060.1	P26373-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL13	ENST00000311528.10	TSL:1 MANE Select	c.93T>G	p.Arg31Arg	synonymous	Exon 2 of 6	ENSP00000307889.5	P26373-1
	RPL13	ENST00000393099.4	TSL:1	c.93T>G	p.Arg31Arg	synonymous	Exon 1 of 5	ENSP00000376811.3	P26373-1
	RPL13	ENST00000487034.5	TSL:1	n.144T>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31302 AN: 152058 Hom.: 3444 Cov.: 34

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.0883

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.215

GnomAD2 exomes AF: 0.167 AC: 38475 AN: 229960 AF XY: 0.168

Gnomad AFR exome AF: 0.278

Gnomad AMR exome AF: 0.104

Gnomad ASJ exome AF: 0.220

Gnomad EAS exome AF: 0.155

Gnomad FIN exome AF: 0.0924

Gnomad NFE exome AF: 0.192

Gnomad OTH exome AF: 0.180

GnomAD4 exome AF: 0.190 AC: 275719 AN: 1452848 Hom.: 27136 Cov.: 33 AF XY: 0.189 AC XY: 136324 AN XY: 722634

African (AFR) AF: 0.289 AC: 9287 AN: 32170

American (AMR) AF: 0.109 AC: 4858 AN: 44372

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 5740 AN: 25900

East Asian (EAS) AF: 0.134 AC: 5244 AN: 39034

South Asian (SAS) AF: 0.153 AC: 13047 AN: 85180

European-Finnish (FIN) AF: 0.0998 AC: 5166 AN: 51762

Middle Eastern (MID) AF: 0.219 AC: 1174 AN: 5366

European-Non Finnish (NFE) AF: 0.198 AC: 219240 AN: 1109054

Other (OTH) AF: 0.199 AC: 11963 AN: 60010

GnomAD4 genome AF: 0.206 AC: 31358 AN: 152166 Hom.: 3467 Cov.: 34 AF XY: 0.199 AC XY: 14812 AN XY: 74386

African (AFR) AF: 0.287 AC: 11925 AN: 41512

American (AMR) AF: 0.149 AC: 2275 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 827 AN: 3470

East Asian (EAS) AF: 0.158 AC: 815 AN: 5162

South Asian (SAS) AF: 0.156 AC: 754 AN: 4826

European-Finnish (FIN) AF: 0.0883 AC: 938 AN: 10618

Middle Eastern (MID) AF: 0.202 AC: 59 AN: 292

European-Non Finnish (NFE) AF: 0.192 AC: 13026 AN: 67960

Other (OTH) AF: 0.215 AC: 454 AN: 2116

Alfa AF: 0.197 Hom.: 1439

Bravo AF: 0.215

Asia WGS AF: 0.135 AC: 468 AN: 3470

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Spondyloepimetaphyseal dysplasia, Isidor-Toutain type (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	12
DANN	Benign	0.80
PhyloP100		0.29
PromoterAI		0.20	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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

Other links and lift over

dbSNP: rs2280370; hg19: chr16-89627460; COSMIC: COSV51951754; COSMIC: COSV51951754;