9-10054522-T-C

Variant names:

• chr9-10054522-T-C
• rs447578
• NM_002839.4:c.-544-20732A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002839.4(PTPRD):​c.-544-20732A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,060 control chromosomes in the GnomAD database, including 2,712 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 0.18 (2712 hom., cov: 32)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRD	NM_002839.4	c.-544-20732A>G		intron_variant	Intron 3 of 45	ENST00000381196.9	NP_002830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRD	ENST00000381196.9	c.-544-20732A>G		intron_variant	Intron 3 of 45	5	NM_002839.4	ENSP00000370593.3
PTPRD	ENST00000463477.5	c.-616-20732A>G		intron_variant	Intron 3 of 16	1		ENSP00000417661.1
PTPRD	ENST00000850942.1	c.-544-20732A>G		intron_variant	Intron 5 of 47			ENSP00000521027.1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26649 AN: 151942 Hom.: 2704 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.0839

Gnomad EAS AF: 0.0151

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.170

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.176 AC: 26691 AN: 152060 Hom.: 2712 Cov.: 32 AF XY: 0.173 AC XY: 12821 AN XY: 74324

African (AFR) AF: 0.273 AC: 11318 AN: 41434

American (AMR) AF: 0.185 AC: 2822 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0839 AC: 291 AN: 3470

East Asian (EAS) AF: 0.0147 AC: 76 AN: 5164

South Asian (SAS) AF: 0.110 AC: 532 AN: 4826

European-Finnish (FIN) AF: 0.143 AC: 1517 AN: 10596

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9645 AN: 67992

Other (OTH) AF: 0.169 AC: 357 AN: 2108

Alfa AF: 0.162 Hom.: 302

Bravo AF: 0.184

Asia WGS AF: 0.0900 AC: 314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.0
DANN	Benign	0.73
PhyloP100		-0.037
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs447578; hg19: chr9-10054522;