9-9800546-G-T

Position:

• chr9-9800546-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002839.4(PTPRD):​c.-367-33695C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 151,914 control chromosomes in the GnomAD database, including 28,868 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.61 (28868 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.452

Genes affected

PTPRD (HGNC:9668): (protein tyrosine phosphatase receptor type D) 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 region, a single transmembrane segment and two tandem intracytoplasmic catalytic domains, and thus represents a receptor-type PTP. The extracellular region of this protein is composed of three Ig-like and eight fibronectin type III-like domains. Studies of the similar genes in chicken and fly suggest the role of this PTP is in promoting neurite growth, and regulating neurons axon guidance. Multiple alternatively spliced transcript variants of this gene have been reported. A related pseudogene has been identified on chromosome 5. [provided by RefSeq, Jan 2010]

ENSG00000230920 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRD	NM_002839.4	c.-367-33695C>A		intron_variant		ENST00000381196.9	NP_002830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRD	ENST00000381196.9	c.-367-33695C>A		intron_variant		5	NM_002839.4	ENSP00000370593.3
PTPRD	ENST00000463477.5	c.-439-33695C>A		intron_variant		1		ENSP00000417661.1
ENSG00000230920	ENST00000449531.1	n.187G>T		splice_region_variant, non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91900 AN: 151796 Hom.: 28813 Cov.: 31

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.871

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.570

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.606 AC: 92014 AN: 151914 Hom.: 28868 Cov.: 31 AF XY: 0.609 AC XY: 45199 AN XY: 74244

Gnomad4 AFR AF: 0.746

Gnomad4 AMR AF: 0.650

Gnomad4 ASJ AF: 0.492

Gnomad4 EAS AF: 0.871

Gnomad4 SAS AF: 0.533

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.511

Gnomad4 OTH AF: 0.574

Alfa AF: 0.495 Hom.: 5270

Bravo AF: 0.624

Asia WGS AF: 0.735 AC: 2553 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.12
DANN	Benign	0.56

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: rs1768881; hg19: chr9-9800546;