NM_000978.4:c.366A>G

Variant names:

• chr17-38850189-T-C
• rs371296702
• NM_000978.4:c.366A>G

Variant summary

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

The NM_000978.4(RPL23):​c.366A>G​(p.Ala122Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000554 in 1,606,604 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A122A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000032 (1 hom.)
• Consequence: RPL23 NM_000978.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.349
• Publications: 0 publications found

Genes affected

RPL23 (HGNC:10316): (ribosomal protein L23) 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 L14P family of ribosomal proteins. It is located in the cytoplasm. This gene has been referred to as rpL17 because the encoded protein shares amino acid identity with ribosomal protein L17 from Saccharomyces cerevisiae; however, its official symbol is RPL23. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 17-38850189-T-C is Benign according to our data. Variant chr17-38850189-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2063593.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.349 with no splicing effect.
• BS2: High AC in GnomAd4 at 43 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000978.4. 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
	RPL23	NM_000978.4	MANE Select	c.366A>G	p.Ala122Ala	synonymous	Exon 5 of 5	NP_000969.1	P62829

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL23	ENST00000479035.7	TSL:1 MANE Select	c.366A>G	p.Ala122Ala	synonymous	Exon 5 of 5	ENSP00000420311.2	P62829
	RPL23	ENST00000584912.5	TSL:1	n.2671A>G		non_coding_transcript_exon	Exon 3 of 3
	RPL23	ENST00000929683.1		c.447A>G	p.Ala149Ala	synonymous	Exon 6 of 6	ENSP00000599742.1

Frequencies

GnomAD3 genomes AF: 0.000283 AC: 43 AN: 151930 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000991

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000810 AC: 20 AN: 246870 AF XY: 0.0000597

Gnomad AFR exome AF: 0.00121

Gnomad AMR exome AF: 0.00

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: 0.000166

GnomAD4 exome AF: 0.0000316 AC: 46 AN: 1454556 Hom.: 1 Cov.: 30 AF XY: 0.0000332 AC XY: 24 AN XY: 723394

African (AFR) AF: 0.00127 AC: 42 AN: 33126

American (AMR) AF: 0.00 AC: 0 AN: 44030

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25990

East Asian (EAS) AF: 0.00 AC: 0 AN: 39506

South Asian (SAS) AF: 0.00 AC: 0 AN: 84546

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53254

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4228

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109902

Other (OTH) AF: 0.0000500 AC: 3 AN: 59974

GnomAD4 genome AF: 0.000283 AC: 43 AN: 152048 Hom.: 0 Cov.: 32 AF XY: 0.000283 AC XY: 21 AN XY: 74310

African (AFR) AF: 0.000989 AC: 41 AN: 41474

American (AMR) AF: 0.0000656 AC: 1 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10562

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67986

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000385

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	-0.52
CADD	Benign	11
DANN	Benign	0.87
PhyloP100		-0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs371296702; hg19: chr17-37006442;