rs749731223

Variant names:

• chr3-23918015-C-T
• rs749731223
• NM_002948.5:c.156C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-23918015-C-T
• chr3-23918015-C-G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_002948.5(RPL15):​c.156C>T​(p.Gly52Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000048 in 1,457,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: RPL15 NM_002948.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.82
• Publications: 1 publications found

Genes affected

RPL15 (HGNC:10306): (ribosomal protein L15) 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 L15E family of ribosomal proteins and a component of the 60S subunit. This gene shares sequence similarity with the yeast ribosomal protein YL10 gene. Elevated expression of this gene has been observed in esophageal tumors and gastric cancer tissues, and deletion of this gene has been observed in a Diamond-Blackfan anemia (DBA) patient. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Mar 2017]

NKIRAS1 (HGNC:17899): (NFKB inhibitor interacting Ras like 1) Predicted to enable GTPase activating protein binding activity. Predicted to be involved in I-kappaB kinase/NF-kappaB signaling. Predicted to act upstream of or within several processes, including Ral protein signal transduction; lung alveolus development; and surfactant homeostasis. Located in cytosol and endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 3-23918015-C-T is Benign according to our data. Variant chr3-23918015-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2183537.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.82 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 7 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002948.5. 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
	RPL15	NM_002948.5	MANE Select	c.156C>T	p.Gly52Gly	synonymous	Exon 2 of 4	NP_002939.2
	RPL15	NM_001253379.2		c.156C>T	p.Gly52Gly	synonymous	Exon 2 of 4	NP_001240308.1	P61313-1
	RPL15	NM_001253380.2		c.156C>T	p.Gly52Gly	synonymous	Exon 1 of 3	NP_001240309.1	P61313-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL15	ENST00000307839.10	TSL:1 MANE Select	c.156C>T	p.Gly52Gly	synonymous	Exon 2 of 4	ENSP00000309334.5	P61313-1
	RPL15	ENST00000354811.5	TSL:1	c.156C>T	p.Gly52Gly	synonymous	Exon 1 of 3	ENSP00000346867.5	P61313-1
	RPL15	ENST00000456530.7	TSL:1	c.156C>T	p.Gly52Gly	synonymous	Exon 2 of 5	ENSP00000398788.2	P61313-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000284 AC: 7 AN: 246146 AF XY: 0.0000150

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000212

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000480 AC: 7 AN: 1457134 Hom.: 0 Cov.: 31 AF XY: 0.00000414 AC XY: 3 AN XY: 725036

African (AFR) AF: 0.00 AC: 0 AN: 33172

American (AMR) AF: 0.000163 AC: 7 AN: 42994

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25820

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 85744

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110500

Other (OTH) AF: 0.00 AC: 0 AN: 60204

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	4.0
DANN	Benign	0.91
PhyloP100		-4.8
PromoterAI		0.0081	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs749731223; hg19: chr3-23959506;