11-67436073-C-T

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005608.3(PTPRCAP):c.281G>A(p.Arg94Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000168 in 1,612,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

PTPRCAP
NM_005608.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0370

Variant links:

Genes affected

PTPRCAP (HGNC:9667): (protein tyrosine phosphatase receptor type C associated protein) The protein encoded by this gene was identified as a transmembrane phosphoprotein specifically associated with tyrosine phosphatase PTPRC/CD45, a key regulator of T- and B-lymphocyte activation. The interaction with PTPRC may be required for the stable expression of this protein. [provided by RefSeq, Jul 2008]

PTPRCAP links:

CORO1B (HGNC:2253): (coronin 1B) Members of the coronin family, such as CORO1B, are WD repeat-containing actin-binding proteins that regulate cell motility (Cai et al., 2005 [PubMed 16027158]).[supplied by OMIM, Mar 2008]

CORO1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05690548).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRCAP	NM_005608.3 link	c.281G>A	p.Arg94Gln	missense_variant	Exon 2 of 2	ENST00000326294.4	NP_005599.1	Q14761
CORO1B	NM_020441.3 link	c.*2303G>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000341356.10	NP_065174.1	Q9BR76A0A024R5K1
CORO1B	NM_001018070.3 link	c.*2303G>A		3_prime_UTR_variant	Exon 12 of 12		NP_001018080.1	Q9BR76A0A024R5K1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PTPRCAP	ENST00000326294.4 link	c.281G>A	p.Arg94Gln	missense_variant	Exon 2 of 2	1	NM_005608.3	ENSP00000325589.3	Q14761
CORO1B	ENST00000341356 link	c.*2303G>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_020441.3	ENSP00000340211.5	Q9BR76
CORO1B	ENST00000616321.4 link	n.*3035G>A		non_coding_transcript_exon_variant	Exon 11 of 11	2		ENSP00000479949.1	A0A087WW53
CORO1B	ENST00000616321.4 link	n.*3035G>A		3_prime_UTR_variant	Exon 11 of 11	2		ENSP00000479949.1	A0A087WW53

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000573

AC:

AN:

244476

Hom.:

AF XY:

0.0000450

AC XY:

AN XY:

133208

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000470

Gnomad NFE exome

AF:

0.000120

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000179

AC:

262

AN:

1460336

Hom.:

Cov.:

AF XY:

0.000183

AC XY:

133

AN XY:

726404

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000570

Gnomad4 NFE exome

AF:

0.000224

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000193

Hom.:

Bravo

AF:

0.0000604

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.0000496

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.281G>A (p.R94Q) alteration is located in exon 2 (coding exon 2) of the PTPRCAP gene. This alteration results from a G to A substitution at nucleotide position 281, causing the arginine (R) at amino acid position 94 to be replaced by a glutamine (Q). 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

0.084

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.73

M_CAP

Benign

0.012

MetaRNN

Benign

0.057

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.5

REVEL

Benign

0.016

Sift

Benign

0.19

Sift4G

Benign

0.47

Polyphen

0.040

Vest4

0.077

MVP

0.17

MPC

0.45

ClinPred

0.072

GERP RS

-2.6

Varity_R

0.053

gMVP

0.072

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over