17-38850224-A-AAAAAT

Position:

• chr17-38850224-A-AAAAAT

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_000978.4(RPL23):​c.341-11_341-10insATTTT 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 0.000599 in 1,586,396 control chromosomes in the GnomAD database, including 8 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0032 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00032 (5 hom.)
• Consequence: RPL23 NM_000978.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0150

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 17-38850224-A-AAAAAT is Benign according to our data. Variant chr17-38850224-A-AAAAAT is described in ClinVar as [Likely_benign]. Clinvar id is 1971298.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 488 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPL23	NM_000978.4	c.341-11_341-10insATTTT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000479035.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPL23	ENST00000479035.7	c.341-11_341-10insATTTT		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000978.4	P1

Frequencies

GnomAD3 genomes AF: 0.00313 AC: 476 AN: 152062 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0105

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000657 AC: 152 AN: 231182 Hom.: 3 AF XY: 0.000499 AC XY: 63 AN XY: 126132

Gnomad AFR exome AF: 0.00786

Gnomad AMR exome AF: 0.000502

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000602

Gnomad SAS exome AF: 0.0000740

Gnomad FIN exome AF: 0.0000946

Gnomad NFE exome AF: 0.000131

Gnomad OTH exome AF: 0.000181

GnomAD4 exome AF: 0.000322 AC: 462 AN: 1434216 Hom.: 5 Cov.: 28 AF XY: 0.000317 AC XY: 226 AN XY: 713496

Gnomad4 AFR exome AF: 0.00868

Gnomad4 AMR exome AF: 0.000698

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000863

Gnomad4 FIN exome AF: 0.0000947

Gnomad4 NFE exome AF: 0.0000963

Gnomad4 OTH exome AF: 0.000678

GnomAD4 genome AF: 0.00321 AC: 488 AN: 152180 Hom.: 3 Cov.: 32 AF XY: 0.00316 AC XY: 235 AN XY: 74418

Gnomad4 AFR AF: 0.0107

Gnomad4 AMR AF: 0.00151

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00142

Asia WGS AF: 0.000578 AC: 2 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 10, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs540966358; hg19: chr17-37006477;