rs1801173

Variant names:

• chr1-3682346-C-T
• rs1801173
• NM_005427.4:c.-20C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005427.4(TP73):​c.-20C>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 0.204 in 1,513,362 control chromosomes in the GnomAD database, including 32,322 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (2804 hom., cov: 34)
  • Exomes 𝑓: 0.21 (29518 hom.)
• Consequence: TP73 NM_005427.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.956
• Publications: 38 publications found

Genes affected

TP73 (HGNC:12003): (tumor protein p73) This gene encodes a member of the p53 family of transcription factors involved in cellular responses to stress and development. It maps to a region on chromosome 1p36 that is frequently deleted in neuroblastoma and other tumors, and thought to contain multiple tumor suppressor genes. The demonstration that this gene is monoallelically expressed (likely from the maternal allele), supports the notion that it is a candidate gene for neuroblastoma. Many transcript variants resulting from alternative splicing and/or use of alternate promoters have been found for this gene, but the biological validity and the full-length nature of some variants have not been determined. [provided by RefSeq, Feb 2011]

TP73 Gene-Disease associations (from GenCC):

• ciliary dyskinesia, primary, 47, and lissencephaly

  Inheritance: AR Classification: STRONG Submitted by: ClinGen, G2P

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-3682346-C-T is Benign according to our data. Variant chr1-3682346-C-T is described in ClinVar as Benign. ClinVar VariationId is 2585655.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TP73	NM_005427.4	c.-20C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 14	ENST00000378295.9	NP_005418.1
TP73	NM_005427.4	c.-20C>T		5_prime_UTR_variant	Exon 2 of 14	ENST00000378295.9	NP_005418.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TP73	ENST00000378295.9	c.-20C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 14	1	NM_005427.4	ENSP00000367545.4
TP73	ENST00000378295.9	c.-20C>T		5_prime_UTR_variant	Exon 2 of 14	1	NM_005427.4	ENSP00000367545.4

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28323 AN: 152084 Hom.: 2801 Cov.: 34

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.196

GnomAD2 exomes AF: 0.202 AC: 30400 AN: 150652 AF XY: 0.196

Gnomad AFR exome AF: 0.132

Gnomad AMR exome AF: 0.278

Gnomad ASJ exome AF: 0.206

Gnomad EAS exome AF: 0.226

Gnomad FIN exome AF: 0.182

Gnomad NFE exome AF: 0.207

Gnomad OTH exome AF: 0.206

GnomAD4 exome AF: 0.205 AC: 279644 AN: 1361158 Hom.: 29518 Cov.: 31 AF XY: 0.203 AC XY: 136017 AN XY: 669512

African (AFR) AF: 0.123 AC: 3789 AN: 30738

American (AMR) AF: 0.281 AC: 9517 AN: 33822

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 4679 AN: 23334

East Asian (EAS) AF: 0.239 AC: 8296 AN: 34764

South Asian (SAS) AF: 0.137 AC: 10307 AN: 75416

European-Finnish (FIN) AF: 0.179 AC: 8575 AN: 47818

Middle Eastern (MID) AF: 0.197 AC: 1080 AN: 5480

European-Non Finnish (NFE) AF: 0.211 AC: 221965 AN: 1053998

Other (OTH) AF: 0.205 AC: 11436 AN: 55788

GnomAD4 genome AF: 0.186 AC: 28344 AN: 152204 Hom.: 2804 Cov.: 34 AF XY: 0.188 AC XY: 13961 AN XY: 74398

African (AFR) AF: 0.128 AC: 5323 AN: 41556

American (AMR) AF: 0.275 AC: 4201 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 689 AN: 3468

East Asian (EAS) AF: 0.217 AC: 1115 AN: 5150

South Asian (SAS) AF: 0.141 AC: 680 AN: 4834

European-Finnish (FIN) AF: 0.187 AC: 1983 AN: 10588

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13796 AN: 67994

Other (OTH) AF: 0.194 AC: 410 AN: 2114

Alfa AF: 0.188 Hom.: 593

Bravo AF: 0.193

Asia WGS AF: 0.172 AC: 597 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Ciliary dyskinesia, primary, 47, and lissencephaly Benign:1

Apr 11, 2023

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.1
DANN	Benign	0.60
PhyloP100		-0.96
PromoterAI		-0.0017	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	polymorphism (auto)

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: rs1801173; hg19: chr1-3598910; COSMIC: COSV60700849; COSMIC: COSV60700849;