17-38850219-A-G

Variant names:

• chr17-38850219-A-G
• rs775649581
• NM_000978.4:c.341-5T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_000978.4(RPL23):​c.341-5T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000283 in 1,589,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000030 (0 hom.)
• Consequence: RPL23 NM_000978.4 splice_region, intron
• Scores: Splicing: ADA: 0.0003874
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.47
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 17-38850219-A-G is Benign according to our data. Variant chr17-38850219-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3700471.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 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.341-5T>C		splice_region intron	N/A	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.341-5T>C		splice_region intron	N/A	ENSP00000420311.2	P62829
	RPL23	ENST00000584912.5	TSL:1	n.2641T>C		non_coding_transcript_exon	Exon 3 of 3
	RPL23	ENST00000577407.5	TSL:2	c.*114T>C		3_prime_UTR	Exon 4 of 4	ENSP00000462773.1	J3KT29

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152056 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000776 AC: 18 AN: 231988 AF XY: 0.000111

Gnomad AFR exome AF: 0.00

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: 0.00

GnomAD4 exome AF: 0.0000299 AC: 43 AN: 1437072 Hom.: 0 Cov.: 30 AF XY: 0.0000532 AC XY: 38 AN XY: 714724

African (AFR) AF: 0.00 AC: 0 AN: 31926

American (AMR) AF: 0.00 AC: 0 AN: 40184

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25352

East Asian (EAS) AF: 0.00 AC: 0 AN: 39358

South Asian (SAS) AF: 0.000529 AC: 43 AN: 81274

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52826

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102662

Other (OTH) AF: 0.00 AC: 0 AN: 59200

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152056 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74274

African (AFR) AF: 0.00 AC: 0 AN: 41376

American (AMR) AF: 0.00 AC: 0 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5206

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

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	13
DANN	Benign	0.88
PhyloP100		2.5

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00039
dbscSNV1_RF	Benign	0.028
SpliceAI score (max)		0.090		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: rs775649581; hg19: chr17-37006472;