11-67436149-G-A

Variant names:

• chr11-67436149-G-A
• rs762585213
• NM_005608.3:c.205C>T

Variant summary

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

The NM_005608.3(PTPRCAP):​c.205C>T​(p.Arg69Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000423 in 1,418,072 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. R69H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: PTPRCAP NM_005608.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.89

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]

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]

ACMG classification

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	c.205C>T	p.Arg69Cys	missense_variant	Exon 2 of 2	ENST00000326294.4	NP_005599.1
CORO1B	NM_020441.3	c.*2227C>T		3_prime_UTR_variant	Exon 11 of 11	ENST00000341356.10	NP_065174.1
CORO1B	NM_001018070.3	c.*2227C>T		3_prime_UTR_variant	Exon 12 of 12		NP_001018080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRCAP	ENST00000326294.4	c.205C>T	p.Arg69Cys	missense_variant	Exon 2 of 2	1	NM_005608.3	ENSP00000325589.3
CORO1B	ENST00000341356	c.*2227C>T		3_prime_UTR_variant	Exon 11 of 11	1	NM_020441.3	ENSP00000340211.5
CORO1B	ENST00000616321.4	n.*2959C>T		non_coding_transcript_exon_variant	Exon 11 of 11	2		ENSP00000479949.1
CORO1B	ENST00000616321.4	n.*2959C>T		3_prime_UTR_variant	Exon 11 of 11	2		ENSP00000479949.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000581 AC: 1 AN: 172030 Hom.: 0 AF XY: 0.0000107 AC XY: 1 AN XY: 93338

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: 0.00

Gnomad NFE exome AF: 0.0000146

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000423 AC: 6 AN: 1418072 Hom.: 0 Cov.: 31 AF XY: 0.00000713 AC XY: 5 AN XY: 701386

Gnomad4 AFR exome AF: 0.0000613

Gnomad4 AMR exome AF: 0.0000263

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000205

Gnomad4 NFE exome AF: 0.00000184

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000315 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000259 AC: 3

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 13, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.205C>T (p.R69C) alteration is located in exon 2 (coding exon 2) of the PTPRCAP gene. This alteration results from a C to T substitution at nucleotide position 205, causing the arginine (R) at amino acid position 69 to be replaced by a cysteine (C). 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	0.33
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.43	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.89	D
M_CAP	Pathogenic	0.40	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	1.5	L
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-7.8	D
REVEL	Uncertain	0.33
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.97	D
Vest4		0.45
MutPred		0.59		Loss of MoRF binding (P = 0.0025);
MVP		0.54
MPC		1.1
ClinPred		1.0	D
GERP RS		4.7
Varity_R		0.70
gMVP		0.41

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

LitVar

Other links and lift over

dbSNP: rs762585213; hg19: chr11-67203620;