9-8331574-A-AAACTTACCATTCCTGAACTGT

Position:

• chr9-8331574-A-AAACTTACCATTCCTGAACTGT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_002839.4(PTPRD):​c.5534+7_5534+8insACAGTTCAGGAATGGTAAGTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 1,607,146 control chromosomes in the GnomAD database, including 18,470 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1929 hom., cov: 0)
  • Exomes 𝑓: 0.13 (16541 hom.)
• Consequence: PTPRD NM_002839.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRD	NM_002839.4	c.5534+7_5534+8insACAGTTCAGGAATGGTAAGTT		splice_region_variant, intron_variant		ENST00000381196.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRD	ENST00000381196.9	c.5534+7_5534+8insACAGTTCAGGAATGGTAAGTT		splice_region_variant, intron_variant		5	NM_002839.4	P1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21227 AN: 151868 Hom.: 1925 Cov.: 0

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.124

GnomAD4 exome AF: 0.134 AC: 194426 AN: 1455162 Hom.: 16541 Cov.: 35 AF XY: 0.134 AC XY: 96820 AN XY: 724272

Gnomad4 AFR exome AF: 0.0959

Gnomad4 AMR exome AF: 0.377

Gnomad4 ASJ exome AF: 0.0953

Gnomad4 EAS exome AF: 0.349

Gnomad4 SAS exome AF: 0.193

Gnomad4 FIN exome AF: 0.145

Gnomad4 NFE exome AF: 0.113

Gnomad4 OTH exome AF: 0.137

GnomAD4 genome AF: 0.140 AC: 21239 AN: 151984 Hom.: 1929 Cov.: 0 AF XY: 0.147 AC XY: 10907 AN XY: 74292

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.346

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.126

Alfa AF: 0.0876 Hom.: 255

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3215098; hg19: chr9-8331574;