16-89561263-C-T

Variant names:

• chr16-89561263-C-T
• rs174035
• NM_000977.4:c.141C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_000977.4(RPL13):​c.141C>T​(p.Ala47Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 1,553,686 control chromosomes in the GnomAD database, including 28,959 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2289 hom., cov: 34)
  • Exomes 𝑓: 0.19 (26670 hom.)
• Consequence: RPL13 NM_000977.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0930
• Publications: 16 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]

SNORD68 (HGNC:32729): (small nucleolar RNA, C/D box 68)

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.21).
• BP6: Variant 16-89561263-C-T is Benign according to our data. Variant chr16-89561263-C-T is described in ClinVar as Benign. ClinVar VariationId is 1327971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.093 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.193 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.141C>T	p.Ala47Ala	synonymous	Exon 3 of 6	NP_000968.2
	RPL13	NM_033251.2		c.141C>T	p.Ala47Ala	synonymous	Exon 2 of 5	NP_150254.1	P26373-1
	RPL13	NM_001243131.1		c.141C>T	p.Ala47Ala	synonymous	Exon 3 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.141C>T	p.Ala47Ala	synonymous	Exon 3 of 6	ENSP00000307889.5	P26373-1
	RPL13	ENST00000393099.4	TSL:1	c.141C>T	p.Ala47Ala	synonymous	Exon 2 of 5	ENSP00000376811.3	P26373-1
	RPL13	ENST00000487034.5	TSL:1	n.355C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25426 AN: 152106 Hom.: 2284 Cov.: 34

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.0893

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.193

GnomAD2 exomes AF: 0.164 AC: 25264 AN: 153978 AF XY: 0.167

Gnomad AFR exome AF: 0.140

Gnomad AMR exome AF: 0.104

Gnomad ASJ exome AF: 0.238

Gnomad EAS exome AF: 0.144

Gnomad FIN exome AF: 0.0952

Gnomad NFE exome AF: 0.201

Gnomad OTH exome AF: 0.194

GnomAD4 exome AF: 0.192 AC: 269238 AN: 1401460 Hom.: 26670 Cov.: 34 AF XY: 0.191 AC XY: 132561 AN XY: 693542

African (AFR) AF: 0.140 AC: 4486 AN: 32066

American (AMR) AF: 0.111 AC: 4135 AN: 37226

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 6060 AN: 25294

East Asian (EAS) AF: 0.125 AC: 4595 AN: 36698

South Asian (SAS) AF: 0.151 AC: 12354 AN: 81664

European-Finnish (FIN) AF: 0.101 AC: 3949 AN: 39258

Middle Eastern (MID) AF: 0.214 AC: 930 AN: 4344

European-Non Finnish (NFE) AF: 0.204 AC: 221337 AN: 1086654

Other (OTH) AF: 0.196 AC: 11392 AN: 58256

GnomAD4 genome AF: 0.167 AC: 25450 AN: 152226 Hom.: 2289 Cov.: 34 AF XY: 0.162 AC XY: 12063 AN XY: 74428

African (AFR) AF: 0.143 AC: 5956 AN: 41560

American (AMR) AF: 0.140 AC: 2142 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 883 AN: 3466

East Asian (EAS) AF: 0.146 AC: 752 AN: 5150

South Asian (SAS) AF: 0.153 AC: 740 AN: 4832

European-Finnish (FIN) AF: 0.0893 AC: 949 AN: 10626

Middle Eastern (MID) AF: 0.182 AC: 53 AN: 292

European-Non Finnish (NFE) AF: 0.195 AC: 13275 AN: 67968

Other (OTH) AF: 0.192 AC: 407 AN: 2116

Alfa AF: 0.121 Hom.: 347

Bravo AF: 0.171

Asia WGS AF: 0.117 AC: 408 AN: 3478

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	-0.21
CADD	Benign	14
DANN	Uncertain	0.98
PhyloP100		0.093
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Mutation Taster		=92/8	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: rs174035; hg19: chr16-89627671;