16-89561263-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000977.4(RPL13):​c.141C>A​(p.Ala47Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,401,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A47A) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: RPL13 NM_000977.4 synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.19).

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>A	p.Ala47Ala	synonymous	Exon 3 of 6	NP_000968.2
	RPL13	NM_033251.2		c.141C>A	p.Ala47Ala	synonymous	Exon 2 of 5	NP_150254.1	P26373-1
	RPL13	NM_001243131.1		c.141C>A	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>A	p.Ala47Ala	synonymous	Exon 3 of 6	ENSP00000307889.5	P26373-1
	RPL13	ENST00000393099.4	TSL:1	c.141C>A	p.Ala47Ala	synonymous	Exon 2 of 5	ENSP00000376811.3	P26373-1
	RPL13	ENST00000487034.5	TSL:1	n.355C>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1401556 Hom.: 0 Cov.: 34 AF XY: 0.00000288 AC XY: 2 AN XY: 693600

African (AFR) AF: 0.0000624 AC: 2 AN: 32066

American (AMR) AF: 0.00 AC: 0 AN: 37232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25294

East Asian (EAS) AF: 0.00 AC: 0 AN: 36698

South Asian (SAS) AF: 0.00 AC: 0 AN: 81676

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39266

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4348

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1086716

Other (OTH) AF: 0.0000172 AC: 1 AN: 58260

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 347

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.19
CADD	Benign	13
DANN	Benign	0.95
PhyloP100		0.093
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9

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;