chr1-3727758-G-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_005427.4(TP73):c.973G>A(p.Ala325Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 1,542,420 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0090 ( 22 hom., cov: 33)
Exomes 𝑓: 0.00087 ( 13 hom. )
Consequence
TP73
NM_005427.4 missense
NM_005427.4 missense
Scores
5
13
Clinical Significance
Conservation
PhyloP100: 2.81
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 Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0050243437).
BP6
?
Variant 1-3727758-G-A is Benign according to our data. Variant chr1-3727758-G-A is described in ClinVar as [Benign]. Clinvar id is 714065.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00902 (1374/152320) while in subpopulation AFR AF= 0.0318 (1321/41572). AF 95% confidence interval is 0.0304. There are 22 homozygotes in gnomad4. There are 636 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 22 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TP73 | NM_005427.4 | c.973G>A | p.Ala325Thr | missense_variant | 8/14 | ENST00000378295.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TP73 | ENST00000378295.9 | c.973G>A | p.Ala325Thr | missense_variant | 8/14 | 1 | NM_005427.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00903 AC: 1375AN: 152202Hom.: 22 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00221 AC: 325AN: 146868Hom.: 2 AF XY: 0.00173 AC XY: 136AN XY: 78528
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GnomAD4 exome AF: 0.000866 AC: 1204AN: 1390100Hom.: 13 Cov.: 31 AF XY: 0.000784 AC XY: 537AN XY: 684984
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GnomAD4 genome ? AF: 0.00902 AC: 1374AN: 152320Hom.: 22 Cov.: 33 AF XY: 0.00854 AC XY: 636AN XY: 74478
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Asia WGS
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3478
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | May 30, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.;.;.;.;.;.;.;T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T;T;.;.;T;T;T;T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;L;L;L;L;L;L;.;.;.;.
MutationTaster
Benign
D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N;N;N;.;.;N;N;N;N
REVEL
Uncertain
Sift
Benign
T;.;T;T;T;.;.;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T;T;T;T;T;T
Polyphen
B;.;B;.;.;.;.;B;.;B;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at