chr1-3630994-T-A

Variant names:

• chr1-3630994-T-A
• rs146569819
• NM_017818.4:c.1364A>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_017818.4(WRAP73):​c.1364A>T​(p.Gln455Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,612,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: WRAP73 NM_017818.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.503
• Publications: 1 publications found

Genes affected

WRAP73 (HGNC:12759): (WD repeat containing, antisense to TP73) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. Studies of the related mouse protein suggest that the encoded protein may play a role in the process of ossification. [provided by RefSeq, Mar 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03725612).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017818.4. 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
	WRAP73	NM_017818.4	MANE Select	c.1364A>T	p.Gln455Leu	missense	Exon 12 of 12	NP_060288.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WRAP73	ENST00000270708.12	TSL:1 MANE Select	c.1364A>T	p.Gln455Leu	missense	Exon 12 of 12	ENSP00000270708.7	Q9P2S5
	WRAP73	ENST00000378322.7	TSL:1	c.*404A>T		3_prime_UTR	Exon 11 of 11	ENSP00000367573.3	A0A0A0MRV3
	WRAP73	ENST00000960493.1		c.1352A>T	p.Gln451Leu	missense	Exon 12 of 12	ENSP00000630552.1

Frequencies

GnomAD3 genomes AF: 0.000131 AC: 20 AN: 152228 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000458

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000360 AC: 9 AN: 250340 AF XY: 0.0000147

Gnomad AFR exome AF: 0.000557

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: 0.0000185 AC: 27 AN: 1460604 Hom.: 0 Cov.: 31 AF XY: 0.00000826 AC XY: 6 AN XY: 726578

African (AFR) AF: 0.000717 AC: 24 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52312

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111896

Other (OTH) AF: 0.0000166 AC: 1 AN: 60378

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152346 Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14 AN XY: 74492

African (AFR) AF: 0.000529 AC: 22 AN: 41592

American (AMR) AF: 0.00 AC: 0 AN: 15306

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.000162

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	8.3
DANN	Benign	0.86
DEOGEN2	Benign	0.0075	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.36	N
PhyloP100		0.50
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.043
Sift	Benign	0.11	T
Sift4G	Benign	0.10	T
Polyphen		0.0	B
Vest4		0.23
MVP		0.12
MPC		0.19
ClinPred		0.0094	T
GERP RS		1.8
Varity_R		0.12
gMVP		0.42
Mutation Taster		=91/9	polymorphism

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: rs146569819; hg19: chr1-3547558;