1-31944881-G-T

Variant names:

• chr1-31944881-G-T
• rs648718
• ENST00000526960.1:n.-25C>A

Variant summary

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

The ENST00000526960.1(PTP4A2):​n.-25C>A 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTP4A2	ENST00000526960.1	n.-25C>A		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;