rs771319678

Variant names:

• chr17-7673250-C-G
• ENST00000455263.6:c.1010G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-7673250-C-G
• chr17-7673250-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_001126113.3(TP53):​c.1010G>C​(p.Arg337Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000299 in 1,339,944 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: TP53 NM_001126113.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135

Genes affected

TP53 (HGNC:11998): (tumor protein p53) This gene encodes a tumor suppressor protein containing transcriptional activation, DNA binding, and oligomerization domains. The encoded protein responds to diverse cellular stresses to regulate expression of target genes, thereby inducing cell cycle arrest, apoptosis, senescence, DNA repair, or changes in metabolism. Mutations in this gene are associated with a variety of human cancers, including hereditary cancers such as Li-Fraumeni syndrome. Alternative splicing of this gene and the use of alternate promoters result in multiple transcript variants and isoforms. Additional isoforms have also been shown to result from the use of alternate translation initiation codons from identical transcript variants (PMIDs: 12032546, 20937277). [provided by RefSeq, Dec 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM1: In a region_of_interest Interaction with HIPK1 (size 270) in uniprot entity P53_HUMAN there are 59 pathogenic changes around while only 5 benign (92%) in NM_001126113.3
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TP53	NM_000546.6	c.993+285G>C		intron_variant	Intron 9 of 10	ENST00000269305.9	NP_000537.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TP53	ENST00000269305.9	c.993+285G>C		intron_variant	Intron 9 of 10	1	NM_000546.6	ENSP00000269305.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000299 AC: 4 AN: 1339944 Hom.: 0 Cov.: 22 AF XY: 0.00000150 AC XY: 1 AN XY: 667170

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000393

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.075	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	.;T;.;.
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.087	N
LIST_S2	Benign	0.47	T;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.52	D;D;D;D
MetaSVM	Pathogenic	0.91	D
PROVEAN	Uncertain	-3.1	.;.;D;.
REVEL	Uncertain	0.36
Sift	Uncertain	0.0010	.;.;D;.
Sift4G	Uncertain	0.010	D;D;D;D
Polyphen		1.0	.;.;D;.
Vest4		0.49
MutPred		0.66		.;.;Gain of catalytic residue at W338 (P = 0.0211);.;
MVP		0.88
ClinPred		0.43	T
GERP RS		0.77

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-7576568;