11-67436248-C-T

Variant names:

• chr11-67436248-C-T
• rs535438022
• NM_005608.3:c.106G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005608.3(PTPRCAP):​c.106G>A​(p.Val36Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,545,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: PTPRCAP NM_005608.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.321

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 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=0.022098184).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRCAP	NM_005608.3	c.106G>A	p.Val36Ile	missense_variant	Exon 2 of 2	ENST00000326294.4	NP_005599.1
CORO1B	NM_020441.3	c.*2128G>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000341356.10	NP_065174.1
CORO1B	NM_001018070.3	c.*2128G>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.106G>A	p.Val36Ile	missense_variant	Exon 2 of 2	1	NM_005608.3	ENSP00000325589.3
CORO1B	ENST00000341356	c.*2128G>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_020441.3	ENSP00000340211.5
CORO1B	ENST00000616321.4	n.*2860G>A		non_coding_transcript_exon_variant	Exon 11 of 11	2		ENSP00000479949.1
CORO1B	ENST00000616321.4	n.*2860G>A		3_prime_UTR_variant	Exon 11 of 11	2		ENSP00000479949.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152190 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

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: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000142 AC: 2 AN: 140378 Hom.: 0 AF XY: 0.0000262 AC XY: 2 AN XY: 76300

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000804

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000108 AC: 15 AN: 1393106 Hom.: 0 Cov.: 31 AF XY: 0.0000102 AC XY: 7 AN XY: 687938

Gnomad4 AFR exome AF: 0.0000315

Gnomad4 AMR exome AF: 0.0000554

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000279

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000740

Gnomad4 OTH exome AF: 0.0000344

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152308 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74462

Gnomad4 AFR AF: 0.0000481

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: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 09, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.106G>A (p.V36I) 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 106, causing the valine (V) at amino acid position 36 to be replaced by an isoleucine (I). 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	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	2.5
DANN	Benign	0.89
DEOGEN2	Benign	0.12	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.52	N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.016
Sift	Benign	0.54	T
Sift4G	Benign	0.42	T
Polyphen		0.010	B
Vest4		0.21
MutPred		0.31		Loss of catalytic residue at V36 (P = 0.0644);
MVP		0.25
MPC		0.39
ClinPred		0.016	T
GERP RS		-1.7
Varity_R		0.019
gMVP		0.33

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: rs535438022; hg19: chr11-67203719;