17-38850487-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_000978.4(RPL23):c.227-12T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000415 in 1,590,452 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00048 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (2 hom.)
• Consequence: RPL23 NM_000978.4 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0001050
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.478

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 17-38850487-A-G is Benign according to our data. Variant chr17-38850487-A-G is described in ClinVar as [Benign]. Clinvar id is 1972183.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 73 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPL23	NM_000978.4	c.227-12T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000479035.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPL23	ENST00000479035.7	c.227-12T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000978.4	P1

Frequencies

GnomAD3 genomes AF: 0.000480 AC: 73 AN: 152202 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00462

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.000959

GnomAD3 exomes AF: 0.000964 AC: 241 AN: 249984 Hom.: 0 AF XY: 0.000858 AC XY: 116 AN XY: 135140

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000586

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00507

Gnomad SAS exome AF: 0.000231

Gnomad FIN exome AF: 0.00509

Gnomad NFE exome AF: 0.000230

Gnomad OTH exome AF: 0.000492

GnomAD4 exome AF: 0.000408 AC: 587 AN: 1438132 Hom.: 2 Cov.: 26 AF XY: 0.000399 AC XY: 286 AN XY: 717086

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000450

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00407

Gnomad4 SAS exome AF: 0.000117

Gnomad4 FIN exome AF: 0.00466

Gnomad4 NFE exome AF: 0.000120

Gnomad4 OTH exome AF: 0.000571

GnomAD4 genome AF: 0.000479 AC: 73 AN: 152320 Hom.: 0 Cov.: 32 AF XY: 0.000685 AC XY: 51 AN XY: 74482

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00463

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00282

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.000949

Alfa AF: 0.000215 Hom.: 0

Bravo AF: 0.000253

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.6
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00011
dbscSNV1_RF	Benign	0.038
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

Publications

LitVar

Other links and lift over

dbSNP: rs138762930; hg19: chr17-37006740;