rs35593266

Variant names:

• chr3-62126467-G-A
• rs35593266
• NM_002841.4:c.616-6135G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002841.4(PTPRG):​c.616-6135G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,208 control chromosomes in the GnomAD database, including 974 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 0.11 (974 hom., cov: 32)
• Consequence: PTPRG NM_002841.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201
• Publications: 3 publications found

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]

ENSG00000302838 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002841.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRG	NM_002841.4	MANE Select	c.616-6135G>A		intron	N/A	NP_002832.3
	PTPRG	NM_001375471.1		c.616-6135G>A		intron	N/A	NP_001362400.1	P23470-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRG	ENST00000474889.6	TSL:1 MANE Select	c.616-6135G>A		intron	N/A	ENSP00000418112.1	P23470-1
	PTPRG	ENST00000295874.14	TSL:1	c.616-6135G>A		intron	N/A	ENSP00000295874.10	P23470-2
	ENSG00000302838	ENST00000789916.1		n.56+3718C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16745 AN: 152090 Hom.: 975 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.0960

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

GnomAD4 genome AF: 0.110 AC: 16766 AN: 152208 Hom.: 974 Cov.: 32 AF XY: 0.112 AC XY: 8349 AN XY: 74420

African (AFR) AF: 0.111 AC: 4618 AN: 41524

American (AMR) AF: 0.108 AC: 1652 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 465 AN: 3472

East Asian (EAS) AF: 0.108 AC: 561 AN: 5182

South Asian (SAS) AF: 0.124 AC: 598 AN: 4820

European-Finnish (FIN) AF: 0.152 AC: 1606 AN: 10588

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 7021 AN: 68006

Other (OTH) AF: 0.0950 AC: 201 AN: 2116

Alfa AF: 0.105 Hom.: 1443

Bravo AF: 0.106

Asia WGS AF: 0.105 AC: 366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	16
DANN	Benign	0.85
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs35593266; hg19: chr3-62112141;