chr11-67436179-G-T

Variant names:

• chr11-67436179-G-T
• rs780094269
• NM_005608.3:c.175C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005608.3(PTPRCAP):​c.175C>A​(p.Arg59Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000712 in 1,404,244 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R59C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: PTPRCAP NM_005608.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.87
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.175C>A	p.Arg59Ser	missense	Exon 2 of 2	NP_005599.1	Q14761
	CORO1B	NM_020441.3	MANE Select	c.*2197C>A		3_prime_UTR	Exon 11 of 11	NP_065174.1	Q9BR76
	CORO1B	NM_001018070.3		c.*2197C>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.175C>A	p.Arg59Ser	missense	Exon 2 of 2	ENSP00000325589.3	Q14761
	CORO1B	ENST00000341356.10	TSL:1 MANE Select	c.*2197C>A		3_prime_UTR	Exon 11 of 11	ENSP00000340211.5	Q9BR76
	CORO1B	ENST00000616321.4	TSL:2	n.*2929C>A		non_coding_transcript_exon	Exon 11 of 11	ENSP00000479949.1	A0A087WW53

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.12e-7 AC: 1 AN: 1404244 Hom.: 0 Cov.: 31 AF XY: 0.00000144 AC XY: 1 AN XY: 693810

African (AFR) AF: 0.00 AC: 0 AN: 32112

American (AMR) AF: 0.00 AC: 0 AN: 36510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25112

East Asian (EAS) AF: 0.00 AC: 0 AN: 36500

South Asian (SAS) AF: 0.00 AC: 0 AN: 80346

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46080

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5658

European-Non Finnish (NFE) AF: 9.23e-7 AC: 1 AN: 1083678

Other (OTH) AF: 0.00 AC: 0 AN: 58248

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Benign	-0.00027	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.069	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.9
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Benign	0.18
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.015	D
Polyphen		0.99	D
Vest4		0.40
MutPred		0.27		Loss of MoRF binding (P = 0.0114)
MVP		0.48
MPC		0.88
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.64
gMVP		0.46
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs780094269; hg19: chr11-67203650;