11-67436190-C-T

Variant names:

• chr11-67436190-C-T
• rs536852844
• NM_005608.3:c.164G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005608.3(PTPRCAP):​c.164G>A​(p.Arg55His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000122 in 1,553,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: PTPRCAP NM_005608.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.641
• Publications: 0 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.053009182).

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.164G>A	p.Arg55His	missense	Exon 2 of 2	NP_005599.1	Q14761
	CORO1B	NM_020441.3	MANE Select	c.*2186G>A		3_prime_UTR	Exon 11 of 11	NP_065174.1	Q9BR76
	CORO1B	NM_001018070.3		c.*2186G>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.164G>A	p.Arg55His	missense	Exon 2 of 2	ENSP00000325589.3	Q14761
	CORO1B	ENST00000341356.10	TSL:1 MANE Select	c.*2186G>A		3_prime_UTR	Exon 11 of 11	ENSP00000340211.5	Q9BR76
	CORO1B	ENST00000616321.4	TSL:2	n.*2918G>A		non_coding_transcript_exon	Exon 11 of 11	ENSP00000479949.1	A0A087WW53

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

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: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000670 AC: 10 AN: 149198 AF XY: 0.0000618

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000884

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000161

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000123 AC: 173 AN: 1401304 Hom.: 0 Cov.: 31 AF XY: 0.000121 AC XY: 84 AN XY: 692146

African (AFR) AF: 0.000125 AC: 4 AN: 31988

American (AMR) AF: 0.00 AC: 0 AN: 36270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25102

East Asian (EAS) AF: 0.00 AC: 0 AN: 36278

South Asian (SAS) AF: 0.0000250 AC: 2 AN: 80098

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45100

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5646

European-Non Finnish (NFE) AF: 0.000152 AC: 165 AN: 1082612

Other (OTH) AF: 0.0000344 AC: 2 AN: 58210

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152334 Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8 AN XY: 74480

African (AFR) AF: 0.000192 AC: 8 AN: 41582

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000854 Hom.: 0

Bravo AF: 0.000140

ExAC AF: 0.00000899 AC: 1

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.64
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.040
Sift	Benign	0.12	T
Sift4G	Uncertain	0.025	D
Polyphen		0.049	B
Vest4		0.14
MutPred		0.27		Loss of MoRF binding (P = 0.0122)
MVP		0.12
MPC		0.99
ClinPred		0.11	T
GERP RS		1.4
Varity_R		0.046
gMVP		0.25
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs536852844; hg19: chr11-67203661;