Genetic Variant TP73:c.-30G>T (chr1-3682336-G-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005427.4(TP73):c.-30G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000285 in 1,495,916 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00027 ( 2 hom. )

Consequence

TP73
NM_005427.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.399

Publications

39 publications found

Variant links:

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

TP73 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TP73	NM_005427.4	MANE Select	c.-30G>T	5_prime_UTR	Exon 2 of 14	NP_005418.1
TP73	NM_001204187.2		c.-30G>T	5_prime_UTR	Exon 2 of 12	NP_001191116.1
TP73	NM_001204188.2		c.-30G>T	5_prime_UTR	Exon 2 of 12	NP_001191117.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TP73	ENST00000378295.9	TSL:1 MANE Select	c.-30G>T	5_prime_UTR	Exon 2 of 14	ENSP00000367545.4
TP73	ENST00000713571.1		n.83G>T	non_coding_transcript_exon	Exon 2 of 5
TP73	ENST00000713570.1		c.-30G>T	5_prime_UTR	Exon 2 of 14	ENSP00000518863.1

Frequencies

GnomAD3 genomes

AF:

0.000408

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.000329

AC:

AN:

136584

AF XY:

0.000456

show subpopulations

Gnomad AFR exome

AF:

0.000245

Gnomad AMR exome

AF:

0.000663

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000302

Gnomad OTH exome

AF:

0.000817

GnomAD4 exome

AF:

0.000270

AC:

363

AN:

1343684

Hom.:

Cov.:

AF XY:

0.000299

AC XY:

197

AN XY:

659278

show subpopulations

African (AFR)

AF:

0.000332

AC:

AN:

30090

American (AMR)

AF:

0.000772

AC:

AN:

32364

Ashkenazi Jewish (ASJ)

AF:

0.0000442

AC:

AN:

22608

East Asian (EAS)

AF:

0.00

AC:

AN:

33818

South Asian (SAS)

AF:

0.000437

AC:

AN:

73290

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47278

Middle Eastern (MID)

AF:

0.00886

AC:

AN:

5416

European-Non Finnish (NFE)

AF:

0.000195

AC:

204

AN:

1043870

Other (OTH)

AF:

0.000783

AC:

AN:

54950

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

105

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:

0.000414

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

41554

American (AMR)

AF:

0.00137

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.000621

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000294

AC:

AN:

68000

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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:

0.000463

Hom.:

286

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

1.7

(source)

DANN

Benign

0.71

PhyloP100

0.40

PromoterAI

0.0023

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=299/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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