11-67436148-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005608.3(PTPRCAP):c.206G>A(p.Arg69His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000439 in 1,571,328 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R69C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

PTPRCAP
NM_005608.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.10

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRCAP	NM_005608.3 link	c.206G>A	p.Arg69His	missense_variant	Exon 2 of 2	ENST00000326294.4	NP_005599.1	Q14761
CORO1B	NM_020441.3 link	c.*2228G>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000341356.10	NP_065174.1	Q9BR76A0A024R5K1
CORO1B	NM_001018070.3 link	c.*2228G>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.206G>A	p.Arg69His	missense_variant	Exon 2 of 2	1	NM_005608.3	ENSP00000325589.3	Q14761
CORO1B	ENST00000341356 link	c.*2228G>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_020441.3	ENSP00000340211.5	Q9BR76
CORO1B	ENST00000616321.4 link	n.*2960G>A		non_coding_transcript_exon_variant	Exon 11 of 11	2		ENSP00000479949.1	A0A087WW53
CORO1B	ENST00000616321.4 link	n.*2960G>A		3_prime_UTR_variant	Exon 11 of 11	2		ENSP00000479949.1	A0A087WW53

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000230

AC:

AN:

174058

Hom.:

AF XY:

0.0000318

AC XY:

AN XY:

94370

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000375

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000747

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000143

Gnomad OTH exome

AF:

0.000215

GnomAD4 exome

AF:

0.0000437

AC:

AN:

1419098

Hom.:

Cov.:

AF XY:

0.0000442

AC XY:

AN XY:

701928

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000523

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000637

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000205

Gnomad4 NFE exome

AF:

0.0000257

Gnomad4 OTH exome

AF:

0.000102

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.0000344

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 18, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.206G>A (p.R69H) 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 206, causing the arginine (R) at amino acid position 69 to be replaced by a histidine (H). 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

0.17

BayesDel_addAF

Benign

-0.032

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.39

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.86

M_CAP

Pathogenic

0.32

MetaRNN

Uncertain

0.47

MetaSVM

Uncertain

-0.23

MutationAssessor

Benign

1.5

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-4.9

REVEL

Uncertain

0.32

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.21

MVP

0.74

MPC

0.99

ClinPred

0.92

GERP RS

4.7

Varity_R

0.52

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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