1-31944881-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The 1-31944881-G-T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 152,224 control chromosomes in the GnomAD database, including 37,486 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 0.69 (37474 hom., cov: 33)
  • Exomes 𝑓: 0.58 (12 hom.)
• Consequence: PTP4A2 ENST00000526960.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.322

Genes affected

PTP4A2 (HGNC:9635): (protein tyrosine phosphatase 4A2) The protein encoded by this gene belongs to a small class of the protein tyrosine phosphatase (PTP) family. PTPs are cell signaling molecules that play regulatory roles in a variety of cellular processes. PTPs in this class contain a protein tyrosine phosphatase catalytic domain and a characteristic C-terminal prenylation motif. This PTP has been shown to primarily associate with plasmic and endosomal membrane through its C-terminal prenylation. This PTP was found to interact with the beta-subunit of Rab geranylgeranyltransferase II (beta GGT II), and thus may function as a regulator of GGT II activity. Overexpression of this gene in mammalian cells conferred a transformed phenotype, which suggested its role in tumorigenesis. Alternatively spliced transcript variants have been described. Related pseudogenes exist on chromosomes 11, 12 and 17. [provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTP4A2	ENST00000526960.1			upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.685 AC: 104135 AN: 152016 Hom.: 37401 Cov.: 33

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.915

Gnomad SAS AF: 0.786

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.669

GnomAD4 exome AF: 0.580 AC: 51 AN: 88 Hom.: 12 Cov.: 0 AF XY: 0.574 AC XY: 39 AN XY: 68

Gnomad4 AFR exome AF: 0.875

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.500

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.530

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.685 AC: 104270 AN: 152136 Hom.: 37474 Cov.: 33 AF XY: 0.688 AC XY: 51132 AN XY: 74362

Gnomad4 AFR AF: 0.889

Gnomad4 AMR AF: 0.716

Gnomad4 ASJ AF: 0.638

Gnomad4 EAS AF: 0.914

Gnomad4 SAS AF: 0.787

Gnomad4 FIN AF: 0.540

Gnomad4 NFE AF: 0.556

Gnomad4 OTH AF: 0.673

Alfa AF: 0.586 Hom.: 36596

Bravo AF: 0.705

Asia WGS AF: 0.861 AC: 2992 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	7.2
Dann	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs648718; hg19: chr1-32410482;