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1-3727123-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_005427.4(TP73):c.741G>A(p.Thr247=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000814 in 1,611,680 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00065 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00083 ( 1 hom. )

Consequence

TP73
NM_005427.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.94
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-3727123-G-A is Benign according to our data. Variant chr1-3727123-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 719698.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.94 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TP73NM_005427.4 linkuse as main transcriptc.741G>A p.Thr247= synonymous_variant 7/14 ENST00000378295.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TP73ENST00000378295.9 linkuse as main transcriptc.741G>A p.Thr247= synonymous_variant 7/141 NM_005427.4 P1O15350-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000651
AC:
99
AN:
152092
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000338
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000655
Gnomad ASJ
AF:
0.00115
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000985
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000679
AC:
169
AN:
248886
Hom.:
0
AF XY:
0.000785
AC XY:
106
AN XY:
134994
show subpopulations
Gnomad AFR exome
AF:
0.000311
Gnomad AMR exome
AF:
0.000609
Gnomad ASJ exome
AF:
0.00121
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000818
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000912
Gnomad OTH exome
AF:
0.000661
GnomAD4 exome
AF:
0.000831
AC:
1213
AN:
1459470
Hom.:
1
Cov.:
31
AF XY:
0.000837
AC XY:
608
AN XY:
726030
show subpopulations
Gnomad4 AFR exome
AF:
0.000269
Gnomad4 AMR exome
AF:
0.000515
Gnomad4 ASJ exome
AF:
0.000845
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000824
Gnomad4 FIN exome
AF:
0.000115
Gnomad4 NFE exome
AF:
0.000944
Gnomad4 OTH exome
AF:
0.000547
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000650
AC:
99
AN:
152210
Hom.:
0
Cov.:
33
AF XY:
0.000578
AC XY:
43
AN XY:
74436
show subpopulations
Gnomad4 AFR
AF:
0.000337
Gnomad4 AMR
AF:
0.000654
Gnomad4 ASJ
AF:
0.00115
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000621
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000986
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000900
Hom.:
0
Bravo
AF:
0.000669
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeAug 16, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.56
Cadd
Benign
2.0
Dann
Benign
0.76

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs140541850; hg19: chr1-3643687; API