3-61989748-A-T

Position:

• chr3-61989748-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002841.4(PTPRG):​c.314A>T​(p.Asp105Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTPRG NM_002841.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.68

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33152872).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRG	NM_002841.4	c.314A>T	p.Asp105Val	missense_variant	3/30	ENST00000474889.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRG	ENST00000474889.6	c.314A>T	p.Asp105Val	missense_variant	3/30	1	NM_002841.4	A1
PTPRG	ENST00000295874.14	c.314A>T	p.Asp105Val	missense_variant	3/29	1		P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 02, 2022

The c.314A>T (p.D105V) alteration is located in exon 3 (coding exon 3) of the PTPRG gene. This alteration results from a A to T substitution at nucleotide position 314, causing the aspartic acid (D) at amino acid position 105 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	22
DANN	Uncertain	0.99
Eigen	Benign	0.018
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.83	T;D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.2	L;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.5	D;D
REVEL	Benign	0.18
Sift	Benign	0.055	T;T
Sift4G	Uncertain	0.011	D;D
Polyphen		0.0030	B;B
Vest4		0.47
MutPred		0.55		Gain of catalytic residue at D105 (P = 0.0042);Gain of catalytic residue at D105 (P = 0.0042);
MVP		0.63
MPC		0.33
ClinPred		0.97	D
GERP RS		4.7
Varity_R		0.57
gMVP		0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-61975422;