NM_005427.4:c.519C>T

Variant names:

• chr1-3722110-C-T
• rs1801174
• NM_005427.4:c.519C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_005427.4(TP73):​c.519C>T​(p.Thr173Thr) 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
• Publications: 29 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005427.4. 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
	TP73	NM_005427.4	MANE Select	c.519C>T	p.Thr173Thr	synonymous	Exon 5 of 14	NP_005418.1
	TP73	NM_001126240.3		c.372C>T	p.Thr124Thr	synonymous	Exon 3 of 12	NP_001119712.1
	TP73	NM_001204192.2		c.306C>T	p.Thr102Thr	synonymous	Exon 3 of 12	NP_001191121.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TP73	ENST00000378295.9	TSL:1 MANE Select	c.519C>T	p.Thr173Thr	synonymous	Exon 5 of 14	ENSP00000367545.4
	TP73	ENST00000378288.8	TSL:1	c.372C>T	p.Thr124Thr	synonymous	Exon 3 of 12	ENSP00000367537.4
	TP73	ENST00000378285.5	TSL:1	c.372C>T	p.Thr124Thr	synonymous	Exon 3 of 11	ENSP00000367534.1

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

GnomAD2 exomes AF: 0.804 AC: 200645 AN: 249628 AF XY: 0.813

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 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

African (AFR) AF: 0.764 AC: 25556 AN: 33464

American (AMR) AF: 0.641 AC: 28645 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.928 AC: 24248 AN: 26118

East Asian (EAS) AF: 0.509 AC: 20205 AN: 39674

South Asian (SAS) AF: 0.760 AC: 65527 AN: 86234

European-Finnish (FIN) AF: 0.853 AC: 44626 AN: 52340

Middle Eastern (MID) AF: 0.922 AC: 5313 AN: 5762

European-Non Finnish (NFE) AF: 0.895 AC: 994832 AN: 1111772

Other (OTH) AF: 0.856 AC: 51642 AN: 60362

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

African (AFR) AF: 0.771 AC: 31994 AN: 41510

American (AMR) AF: 0.726 AC: 11093 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.938 AC: 3255 AN: 3472

East Asian (EAS) AF: 0.522 AC: 2693 AN: 5160

South Asian (SAS) AF: 0.745 AC: 3596 AN: 4828

European-Finnish (FIN) AF: 0.859 AC: 9113 AN: 10612

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.896 AC: 60937 AN: 68020

Other (OTH) AF: 0.848 AC: 1791 AN: 2112

Alfa AF: 0.853 Hom.: 59953

Bravo AF: 0.812

Asia WGS AF: 0.632 AC: 2197 AN: 3478

EpiCase AF: 0.903

EpiControl AF: 0.907

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Ciliary dyskinesia, primary, 47, and lissencephaly (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	2.1
DANN	Benign	0.94
PhyloP100		-0.15
Mutation Taster		=100/0	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: rs1801174; hg19: chr1-3638674; COSMIC: COSV60698339;