3-61562327-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_002841.4(PTPRG):c.40C>T(p.Leu14=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00252 in 1,613,682 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (45 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (39 hom.)
• Consequence: PTPRG NM_002841.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.70

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 3-61562327-C-T is Benign according to our data. Variant chr3-61562327-C-T is described in ClinVar as [Benign]. Clinvar id is 708655.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.7 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0137 (2085/152232) while in subpopulation AFR AF= 0.0471 (1959/41554). AF 95% confidence interval is 0.0454. There are 45 homozygotes in gnomad4. There are 1000 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 45 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRG	NM_002841.4	c.40C>T	p.Leu14=	synonymous_variant	1/30	ENST00000474889.6
PTPRG	NM_001375471.1	c.40C>T	p.Leu14=	synonymous_variant	1/29
PTPRG	XM_017006961.2	c.40C>T	p.Leu14=	synonymous_variant	1/31
PTPRG	XM_017006963.2	c.40C>T	p.Leu14=	synonymous_variant	1/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRG	ENST00000474889.6	c.40C>T	p.Leu14=	synonymous_variant	1/30	1	NM_002841.4	A1
PTPRG	ENST00000295874.14	c.40C>T	p.Leu14=	synonymous_variant	1/29	1		P4
PTPRG	ENST00000495879.1	n.759C>T		non_coding_transcript_exon_variant	1/3	1
PTPRG	ENST00000475527.1	n.477C>T		non_coding_transcript_exon_variant	1/2	5

Frequencies

GnomAD3 genomes AF: 0.0137 AC: 2083 AN: 152114 Hom.: 45 Cov.: 32

Gnomad AFR AF: 0.0472

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00602

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00957

GnomAD3 exomes AF: 0.00359 AC: 900 AN: 250548 Hom.: 18 AF XY: 0.00245 AC XY: 332 AN XY: 135522

Gnomad AFR exome AF: 0.0488

Gnomad AMR exome AF: 0.00246

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000886

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00136 AC: 1989 AN: 1461450 Hom.: 39 Cov.: 31 AF XY: 0.00113 AC XY: 820 AN XY: 727058

Gnomad4 AFR exome AF: 0.0486

Gnomad4 AMR exome AF: 0.00268

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.0000315

Gnomad4 OTH exome AF: 0.00315

GnomAD4 genome AF: 0.0137 AC: 2085 AN: 152232 Hom.: 45 Cov.: 32 AF XY: 0.0134 AC XY: 1000 AN XY: 74436

Gnomad4 AFR AF: 0.0471

Gnomad4 AMR AF: 0.00601

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.00947

Alfa AF: 0.00649 Hom.: 15

Bravo AF: 0.0155

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 20, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	14
Dann	Benign	0.97

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs77802872; hg19: chr3-61548001;