rs1801174

chr1-3722110-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_005427.4(TP73):c.519C>T(p.Thr173=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.86 in 1,612,596 control chromosomes in the GnomAD database, including 602,217 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.83 (52538 hom., cov: 34)
  • Exomes 𝑓: 0.86 (549679 hom.)
• Consequence: TP73 NM_005427.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.149

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 1-3722110-C-T is Benign according to our data. Variant chr1-3722110-C-T is described in ClinVar as [Benign]. Clinvar id is 2585656.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.149 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TP73	NM_005427.4	c.519C>T	p.Thr173=	synonymous_variant	5/14	ENST00000378295.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TP73	ENST00000378295.9	c.519C>T	p.Thr173=	synonymous_variant	5/14	1	NM_005427.4	P1

Frequencies

GnomAD3 genomes AF: 0.826 AC: 125563 AN: 152090 Hom.: 52513 Cov.: 34

Gnomad AFR AF: 0.771

Gnomad AMI AF: 0.975

Gnomad AMR AF: 0.726

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.859

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.896

Gnomad OTH AF: 0.850

GnomAD3 exomes AF: 0.804 AC: 200645 AN: 249628 Hom.: 82730 AF XY: 0.813 AC XY: 110104 AN XY: 135502

Gnomad AFR exome AF: 0.769

Gnomad AMR exome AF: 0.629

Gnomad ASJ exome AF: 0.929

Gnomad EAS exome AF: 0.514

Gnomad SAS exome AF: 0.761

Gnomad FIN exome AF: 0.858

Gnomad NFE exome AF: 0.897

Gnomad OTH exome AF: 0.852

GnomAD4 exome AF: 0.863 AC: 1260594 AN: 1460388 Hom.: 549679 Cov.: 68 AF XY: 0.862 AC XY: 625980 AN XY: 726476

Gnomad4 AFR exome AF: 0.764

Gnomad4 AMR exome AF: 0.641

Gnomad4 ASJ exome AF: 0.928

Gnomad4 EAS exome AF: 0.509

Gnomad4 SAS exome AF: 0.760

Gnomad4 FIN exome AF: 0.853

Gnomad4 NFE exome AF: 0.895

Gnomad4 OTH exome AF: 0.856

GnomAD4 genome AF: 0.825 AC: 125638 AN: 152208 Hom.: 52538 Cov.: 34 AF XY: 0.819 AC XY: 60961 AN XY: 74424

Gnomad4 AFR AF: 0.771

Gnomad4 AMR AF: 0.726

Gnomad4 ASJ AF: 0.938

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.745

Gnomad4 FIN AF: 0.859

Gnomad4 NFE AF: 0.896

Gnomad4 OTH AF: 0.848

Alfa AF: 0.866 Hom.: 39086

Bravo AF: 0.812

Asia WGS AF: 0.632 AC: 2197 AN: 3478

EpiCase AF: 0.903

EpiControl AF: 0.907

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	2.1
Dann	Benign	0.94

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

LitVar

Other links and lift over

dbSNP: rs1801174; hg19: chr1-3638674; COSMIC: COSV60698339;