chr11-67436326-C-T

Variant names:

• chr11-67436326-C-T
• rs758359868
• NM_005608.3:c.28G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005608.3(PTPRCAP):​c.28G>A​(p.Gly10Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000212 in 1,507,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G10W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: PTPRCAP NM_005608.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13695827).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005608.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRCAP	NM_005608.3	MANE Select	c.28G>A	p.Gly10Arg	missense	Exon 2 of 2	NP_005599.1	Q14761
	CORO1B	NM_020441.3	MANE Select	c.*2050G>A		3_prime_UTR	Exon 11 of 11	NP_065174.1	Q9BR76
	CORO1B	NM_001018070.3		c.*2050G>A		3_prime_UTR	Exon 12 of 12	NP_001018080.1	Q9BR76

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRCAP	ENST00000326294.4	TSL:1 MANE Select	c.28G>A	p.Gly10Arg	missense	Exon 2 of 2	ENSP00000325589.3	Q14761
	CORO1B	ENST00000341356.10	TSL:1 MANE Select	c.*2050G>A		3_prime_UTR	Exon 11 of 11	ENSP00000340211.5	Q9BR76
	CORO1B	ENST00000616321.4	TSL:2	n.*2782G>A		non_coding_transcript_exon	Exon 11 of 11	ENSP00000479949.1	A0A087WW53

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152196 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000477 AC: 5 AN: 104904 AF XY: 0.0000708

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000259

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000229 AC: 31 AN: 1355186 Hom.: 0 Cov.: 31 AF XY: 0.0000271 AC XY: 18 AN XY: 665240

African (AFR) AF: 0.0000324 AC: 1 AN: 30824

American (AMR) AF: 0.00 AC: 0 AN: 32210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22318

East Asian (EAS) AF: 0.00 AC: 0 AN: 35594

South Asian (SAS) AF: 0.000179 AC: 13 AN: 72678

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38042

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5272

European-Non Finnish (NFE) AF: 0.0000122 AC: 13 AN: 1061946

Other (OTH) AF: 0.0000710 AC: 4 AN: 56302

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152196 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74352

African (AFR) AF: 0.00 AC: 0 AN: 41438

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000435 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000181 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Uncertain	0.42	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		-1.1
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.17
Sift	Benign	0.31	T
Sift4G	Benign	0.31	T
Polyphen		0.85	P
Vest4		0.14
MutPred		0.55		Gain of solvent accessibility (P = 0.0171)
MVP		0.39
MPC		0.32
ClinPred		0.13	T
GERP RS		2.1
Varity_R		0.083
gMVP		0.35
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs758359868; hg19: chr11-67203797; COSMIC: COSV108811426; COSMIC: COSV108811426;