12-70536026-C-T

Variant names:

• chr12-70536026-C-T
• rs201163672
• NM_001109754.4:c.6080G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001109754.4(PTPRB):​c.6080G>A​(p.Arg2027Gln) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000411 in 1,460,468 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: PTPRB NM_001109754.4 missense, splice_region
• Scores: Splicing: ADA: 0.9781
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.92
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 6 AD gene.

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.6080G>A	p.Arg2027Gln	missense splice_region	Exon 29 of 34	NP_001103224.1	P23467-3
	PTPRB	NM_001330204.2		c.5816G>A	p.Arg1939Gln	missense splice_region	Exon 28 of 33	NP_001317133.1	F8VU56
	PTPRB	NM_002837.6		c.5426G>A	p.Arg1809Gln	missense splice_region	Exon 27 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.6080G>A	p.Arg2027Gln	missense splice_region	Exon 29 of 34	ENSP00000334928.6	P23467-3
	PTPRB	ENST00000261266.9	TSL:1	c.5426G>A	p.Arg1809Gln	missense splice_region	Exon 27 of 32	ENSP00000261266.5	P23467-1
	PTPRB	ENST00000538708.5	TSL:1	c.5156G>A	p.Arg1719Gln	missense splice_region	Exon 26 of 31	ENSP00000438927.1	P23467-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000121 AC: 3 AN: 248728 AF XY: 0.0000148

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: 0.00000888

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1460468 Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 4 AN XY: 726476

African (AFR) AF: 0.00 AC: 0 AN: 33444

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5200

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111458

Other (OTH) AF: 0.00 AC: 0 AN: 60280

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000827 AC: 1

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	Pathogenic	0.62
BayesDel_addAF	Uncertain	0.062	T
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	34
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.65	D
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Uncertain	0.42	D
MutationAssessor	Benign	1.8	L
PhyloP100		4.9
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.030	D
Polyphen		1.0	D
Vest4		0.60
MutPred		0.65		Gain of catalytic residue at R1939 (P = 0)
MVP		0.81
MPC		1.1
ClinPred		0.98	D
GERP RS		5.9
Varity_R		0.92
gMVP		0.55
Mutation Taster		=52/48	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.98
dbscSNV1_RF	Benign	0.67
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: rs201163672; hg19: chr12-70929806;