rs377156203

Variant names:

• chr12-70524533-C-G
• rs377156203
• NM_001109754.4:c.6563G>C

Your query was ambiguous. Multiple possible variants found:

• chr12-70524533-C-G
• chr12-70524533-C-T

Variant summary

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

The NM_001109754.4(PTPRB):​c.6563G>C​(p.Arg2188Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,012 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. R2188W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PTPRB NM_001109754.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.85
• Publications: 0 publications found

Genes affected

PTPRB (HGNC:9665): (protein tyrosine phosphatase receptor type B) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP contains an extracellular domain, a single transmembrane segment and one intracytoplasmic catalytic domain, thus belongs to receptor type PTP. The extracellular region of this PTP is composed of multiple fibronectin type_III repeats, which was shown to interact with neuronal receptor and cell adhesion molecules, such as contactin and tenascin C. This protein was also found to interact with sodium channels, and thus may regulate sodium channels by altering tyrosine phosphorylation status. The functions of the interaction partners of this protein implicate the roles of this PTP in cell adhesion, neurite growth, and neuronal differentiation. Alternate transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2011]

PTPRB-AS1 (HGNC:58150):

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_001109754.4. 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
	PTPRB	NM_001109754.4	MANE Select	c.6563G>C	p.Arg2188Pro	missense	Exon 33 of 34	NP_001103224.1	P23467-3
	PTPRB	NM_001330204.2		c.6299G>C	p.Arg2100Pro	missense	Exon 32 of 33	NP_001317133.1	F8VU56
	PTPRB	NM_002837.6		c.5909G>C	p.Arg1970Pro	missense	Exon 31 of 32	NP_002828.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRB	ENST00000334414.11	TSL:1 MANE Select	c.6563G>C	p.Arg2188Pro	missense	Exon 33 of 34	ENSP00000334928.6	P23467-3
	PTPRB	ENST00000261266.9	TSL:1	c.5909G>C	p.Arg1970Pro	missense	Exon 31 of 32	ENSP00000261266.5	P23467-1
	PTPRB	ENST00000538708.5	TSL:1	c.5639G>C	p.Arg1880Pro	missense	Exon 30 of 31	ENSP00000438927.1	P23467-4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461012 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726826

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111298

Other (OTH) AF: 0.00 AC: 0 AN: 60350

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L
PhyloP100		5.8
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.26
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.015	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.50		Loss of MoRF binding (P = 0.0135)
MVP		0.45
MPC		1.4
ClinPred		0.92	D
GERP RS		5.7
Varity_R		0.98
gMVP		0.82
Mutation Taster		=40/60	disease causing

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: rs377156203; hg19: chr12-70918313;