rs10510875

Positions:

• chr3-62130237-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002841.4(PTPRG):​c.616-2365C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 152,280 control chromosomes in the GnomAD database, including 26 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 0.011 (26 hom., cov: 32)
• Consequence: PTPRG NM_002841.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.365

Genes affected

PTPRG (HGNC:9671): (protein tyrosine phosphatase receptor type G) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP possesses an extracellular region, a single transmembrane region, and two tandem intracytoplasmic catalytic domains, and thus represents a receptor-type PTP. The extracellular region of this PTP contains a carbonic anhydrase-like (CAH) domain, which is also found in the extracellular region of PTPRBETA/ZETA. This gene is located in a chromosomal region that is frequently deleted in renal cell carcinoma and lung carcinoma, thus is thought to be a candidate tumor suppressor gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0106 (1612/152280) while in subpopulation SAS AF= 0.0234 (113/4824). AF 95% confidence interval is 0.0199. There are 26 homozygotes in gnomad4. There are 817 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRG	NM_002841.4	c.616-2365C>T		intron_variant		ENST00000474889.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRG	ENST00000474889.6	c.616-2365C>T		intron_variant		1	NM_002841.4	A1
PTPRG	ENST00000295874.14	c.616-2365C>T		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.0106 AC: 1613 AN: 152162 Hom.: 26 Cov.: 32

Gnomad AFR AF: 0.0137

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.00837

Gnomad ASJ AF: 0.0233

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0238

Gnomad FIN AF: 0.00424

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.00745

Gnomad OTH AF: 0.0191

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0106 AC: 1612 AN: 152280 Hom.: 26 Cov.: 32 AF XY: 0.0110 AC XY: 817 AN XY: 74460

Gnomad4 AFR AF: 0.0137

Gnomad4 AMR AF: 0.00836

Gnomad4 ASJ AF: 0.0233

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0234

Gnomad4 FIN AF: 0.00424

Gnomad4 NFE AF: 0.00745

Gnomad4 OTH AF: 0.0189

Alfa AF: 0.0100 Hom.: 3

Bravo AF: 0.0113

Asia WGS AF: 0.00722 AC: 27 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.94
DANN	Benign	0.72

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

Other links and lift over

dbSNP: rs10510875; hg19: chr3-62115911;