rs12489977

Positions:

• chr3-61644340-C-T

Variant summary

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

The NM_002841.4(PTPRG):​c.85+81968C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 151,970 control chromosomes in the GnomAD database, including 9,341 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 0.32 (9341 hom., cov: 32)
• Consequence: PTPRG NM_002841.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.840

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRG	NM_002841.4	c.85+81968C>T		intron_variant		ENST00000474889.6	NP_002832.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRG	ENST00000474889.6	c.85+81968C>T		intron_variant		1	NM_002841.4	ENSP00000418112	A1
PTPRG	ENST00000295874.14	c.85+81968C>T		intron_variant		1		ENSP00000295874	P4
PTPRG	ENST00000495879.1	n.804+81968C>T		intron_variant, non_coding_transcript_variant		1
PTPRG	ENST00000475527.1	n.522+81968C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49264 AN: 151852 Hom.: 9345 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.324 AC: 49250 AN: 151970 Hom.: 9341 Cov.: 32 AF XY: 0.329 AC XY: 24442 AN XY: 74288

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.479

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.398

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.328

Alfa AF: 0.393 Hom.: 5747

Bravo AF: 0.304

Asia WGS AF: 0.446 AC: 1550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.49
DANN	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs12489977; hg19: chr3-61630014;