11-67435885-C-T

Variant names:

• chr11-67435885-C-T
• NM_005608.3:c.469G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005608.3(PTPRCAP):​c.469G>A​(p.Gly157Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: PTPRCAP NM_005608.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.257

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10514316).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRCAP	NM_005608.3	c.469G>A	p.Gly157Ser	missense_variant	Exon 2 of 2	ENST00000326294.4	NP_005599.1
CORO1B	NM_020441.3	c.*2491G>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000341356.10	NP_065174.1
CORO1B	NM_001018070.3	c.*2491G>A		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.469G>A	p.Gly157Ser	missense_variant	Exon 2 of 2	1	NM_005608.3	ENSP00000325589.3
CORO1B	ENST00000341356	c.*2491G>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_020441.3	ENSP00000340211.5
CORO1B	ENST00000616321.4	n.*3223G>A		non_coding_transcript_exon_variant	Exon 11 of 11	2		ENSP00000479949.1
CORO1B	ENST00000616321.4	n.*3223G>A		3_prime_UTR_variant	Exon 11 of 11	2		ENSP00000479949.1

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

Mar 21, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.469G>A (p.G157S) 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 469, causing the glycine (G) at amino acid position 157 to be replaced by a serine (S). 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	0.095
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.095
Sift	Benign	0.058	T
Sift4G	Benign	0.078	T
Polyphen		0.57	P
Vest4		0.19
MutPred		0.098		Gain of phosphorylation at G157 (P = 0.0148);
MVP		0.24
MPC		0.35
ClinPred		0.32	T
GERP RS		3.9
Varity_R		0.14
gMVP		0.045

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: chr11-67203356;