12-70544603-T-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001109754.4(PTPRB):c.5448A>G(p.Pro1816=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00525 in 1,610,850 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0044 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0053 (26 hom.)
• Consequence: PTPRB NM_001109754.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -6.44

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]

LOC105369828 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 12-70544603-T-C is Benign according to our data. Variant chr12-70544603-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 784303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-6.44 with no splicing effect.
• BS2: High AC in GnomAd at 670 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRB	NM_001109754.4	c.5448A>G	p.Pro1816=	synonymous_variant	22/34	ENST00000334414.11
LOC105369828	XR_001749196.2	n.10007-13377T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRB	ENST00000334414.11	c.5448A>G	p.Pro1816=	synonymous_variant	22/34	1	NM_001109754.4	A1

Frequencies

GnomAD3 genomes AF: 0.00440 AC: 670 AN: 152144 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00825

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.000848

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00678

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00406 AC: 997 AN: 245320 Hom.: 6 AF XY: 0.00388 AC XY: 517 AN XY: 133294

Gnomad AFR exome AF: 0.00158

Gnomad AMR exome AF: 0.00531

Gnomad ASJ exome AF: 0.000602

Gnomad EAS exome AF: 0.0000567

Gnomad SAS exome AF: 0.000534

Gnomad FIN exome AF: 0.000794

Gnomad NFE exome AF: 0.00640

Gnomad OTH exome AF: 0.00673

GnomAD4 exome AF: 0.00534 AC: 7793 AN: 1458588 Hom.: 26 Cov.: 30 AF XY: 0.00520 AC XY: 3770 AN XY: 725610

Gnomad4 AFR exome AF: 0.00129

Gnomad4 AMR exome AF: 0.00541

Gnomad4 ASJ exome AF: 0.000499

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000723

Gnomad4 FIN exome AF: 0.000845

Gnomad4 NFE exome AF: 0.00636

Gnomad4 OTH exome AF: 0.00480

GnomAD4 genome AF: 0.00440 AC: 670 AN: 152262 Hom.: 1 Cov.: 32 AF XY: 0.00416 AC XY: 310 AN XY: 74436

Gnomad4 AFR AF: 0.00140

Gnomad4 AMR AF: 0.00824

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.000848

Gnomad4 NFE AF: 0.00678

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00520 Hom.: 2

Bravo AF: 0.00465

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2022	PTPRB: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Apr 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.84
Dann	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs77630153; hg19: chr12-70938383;