rs748265946

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting

The NM_001143992.2(WRAP53):c.-62C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 807,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

WRAP53
NM_001143992.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.390

Publications

1 publications found

Variant links:

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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
dyskeratosis congenita
Inheritance: AD, Unknown Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, ClinGen
telomere syndrome
Inheritance: SD Classification: MODERATE Submitted by: ClinGen

WRAP53 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0000854 (13/152204) while in subpopulation NFE AF = 0.000191 (13/68038). AF 95% confidence interval is 0.000112. There are 0 homozygotes in GnomAd4. There are 4 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143992.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WRAP53	NM_001143992.2	MANE Select	c.-62C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	NP_001137464.1	Q9BUR4
WRAP53	NM_001143992.2	MANE Select	c.-62C>T	5_prime_UTR	Exon 1 of 11	NP_001137464.1	Q9BUR4
WRAP53	NM_018081.2		c.-148C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	NP_060551.2	Q9BUR4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WRAP53	ENST00000396463.7	TSL:1 MANE Select	c.-62C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	ENSP00000379727.3	Q9BUR4
WRAP53	ENST00000316024.9	TSL:1	c.-148C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	ENSP00000324203.5	Q9BUR4
WRAP53	ENST00000534050.5	TSL:1	c.-148C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000434999.1	E9PMG4

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000130

AC:

AN:

655678

Hom.:

Cov.:

AF XY:

0.000124

AC XY:

AN XY:

338608

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

16214

American (AMR)

AF:

0.00

AC:

AN:

22056

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15690

East Asian (EAS)

AF:

0.00

AC:

AN:

32254

South Asian (SAS)

AF:

0.0000192

AC:

AN:

52140

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31534

Middle Eastern (MID)

AF:

0.000407

AC:

AN:

2456

European-Non Finnish (NFE)

AF:

0.000171

AC:

AN:

450466

Other (OTH)

AF:

0.000183

AC:

AN:

32868

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41450

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.0000680

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Dyskeratosis congenita, autosomal recessive 3 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

6.8

(source)

DANN

Benign

0.86

PhyloP100

-0.39

PromoterAI

-0.066

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over