rs17551157

Variant names:

• chr17-7688193-CG-C
• rs17551157
• ENST00000316024.9:c.-449delG

Your query was ambiguous. Multiple possible variants found:

• chr17-7688193-CG-C
• chr17-7688193-CG-CGG
• chr17-7688193-CG-CGGG
• chr17-7688193-CG-CGGGG
• chr17-7688193-CG-CGGGGG
• chr17-7688193-CG-CGGGGGG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000316024.9(WRAP53):​c.-449delG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000326 in 30,686 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.000033 (0 hom.)
• Consequence: WRAP53 ENST00000316024.9 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.171
• Publications: 1 publications found

Genes affected

WRAP53 (HGNC:25522): (WD repeat containing antisense to TP53) This gene encodes an essential component of the telomerase holoenzyme complex, a ribonucleoprotein complex required for telomere synthesis. This protein is enriched in Cajal bodies, nuclear sites of RNP processing that are important for telomerase function. It interacts with dyskerin, TERT and TERC, other components of active telomerase, and with small Cajal body RNAs (scaRNAs), which are involved in modifying splicing RNAs. This mRNA also functions as a p53 antisense transcript, that regulates endogenous p53 mRNA levels and further induction of p53 protein by targeting the 5' untranslated region of p53 mRNA. Alternatively spliced transcript variants which differ only in the 5' UTR have been found for this gene. [provided by RefSeq, Mar 2011]

WRAP53 Gene-Disease associations (from GenCC):

• dyskeratosis congenita, autosomal recessive 3

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• dyskeratosis congenita

  Inheritance: AR, AD Classification: MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000316024.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WRAP53	NM_001143990.2		c.-1-448delG		intron	N/A	NP_001137462.1
	WRAP53	NM_001143991.2		c.-1-448delG		intron	N/A	NP_001137463.1
	WRAP53	NM_018081.2		c.-455delG		upstream_gene	N/A	NP_060551.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WRAP53	ENST00000316024.9	TSL:1	c.-449delG		5_prime_UTR	Exon 1 of 10	ENSP00000324203.5
	WRAP53	ENST00000431639.6	TSL:1	c.-1-448delG		intron	N/A	ENSP00000397219.2
	WRAP53	ENST00000457584.6	TSL:1	c.-1-448delG		intron	N/A	ENSP00000411061.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.0000326 AC: 1 AN: 30686 Hom.: 0 Cov.: 0 AF XY: 0.0000621 AC XY: 1 AN XY: 16112

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 436

American (AMR) AF: 0.00 AC: 0 AN: 3190

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 526

East Asian (EAS) AF: 0.00 AC: 0 AN: 1008

South Asian (SAS) AF: 0.00 AC: 0 AN: 4750

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1156

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 68

European-Non Finnish (NFE) AF: 0.0000557 AC: 1 AN: 17940

Other (OTH) AF: 0.00 AC: 0 AN: 1612

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs17551157; hg19: chr17-7591511;