NM_002841.4:c.191-14294C>T

Variant names:

• chr3-61975331-C-T
• rs7649496
• NM_002841.4:c.191-14294C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002841.4(PTPRG):​c.191-14294C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 152,000 control chromosomes in the GnomAD database, including 22,067 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 0.53 (22067 hom., cov: 32)
• Consequence: PTPRG NM_002841.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145
• Publications: 0 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.646 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRG	NM_002841.4	MANE Select	c.191-14294C>T		intron	N/A	NP_002832.3
	PTPRG	NM_001375471.1		c.191-14294C>T		intron	N/A	NP_001362400.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRG	ENST00000474889.6	TSL:1 MANE Select	c.191-14294C>T		intron	N/A	ENSP00000418112.1
	PTPRG	ENST00000295874.14	TSL:1	c.191-14294C>T		intron	N/A	ENSP00000295874.10

Frequencies

GnomAD3 genomes AF: 0.534 AC: 81039 AN: 151882 Hom.: 22058 Cov.: 32

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.533 AC: 81085 AN: 152000 Hom.: 22067 Cov.: 32 AF XY: 0.530 AC XY: 39404 AN XY: 74304

African (AFR) AF: 0.653 AC: 27033 AN: 41428

American (AMR) AF: 0.416 AC: 6353 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1926 AN: 3470

East Asian (EAS) AF: 0.423 AC: 2186 AN: 5166

South Asian (SAS) AF: 0.533 AC: 2571 AN: 4820

European-Finnish (FIN) AF: 0.473 AC: 4994 AN: 10566

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.506 AC: 34355 AN: 67960

Other (OTH) AF: 0.525 AC: 1107 AN: 2108

Alfa AF: 0.510 Hom.: 10821

Bravo AF: 0.532

Asia WGS AF: 0.505 AC: 1761 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.9
DANN	Benign	0.25
PhyloP100		0.14
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: rs7649496; hg19: chr3-61961005;