9-9603122-A-T

Variant names:

• chr9-9603122-A-T
• rs10977865
• NM_002839.4:c.-286-28341T>A

Variant summary

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

The NM_002839.4(PTPRD):​c.-286-28341T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 151,968 control chromosomes in the GnomAD database, including 18,240 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 0.48 (18240 hom., cov: 31)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186
• Publications: 1 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRD	NM_002839.4	c.-286-28341T>A		intron_variant	Intron 7 of 45	ENST00000381196.9	NP_002830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRD	ENST00000381196.9	c.-286-28341T>A		intron_variant	Intron 7 of 45	5	NM_002839.4	ENSP00000370593.3
PTPRD	ENST00000463477.5	c.-358-28341T>A		intron_variant	Intron 7 of 16	1		ENSP00000417661.1
PTPRD	ENST00000850942.1	c.-286-28341T>A		intron_variant	Intron 9 of 47			ENSP00000521027.1

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73096 AN: 151850 Hom.: 18225 Cov.: 31

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.497

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

GnomAD4 genome AF: 0.481 AC: 73150 AN: 151968 Hom.: 18240 Cov.: 31 AF XY: 0.474 AC XY: 35214 AN XY: 74254

African (AFR) AF: 0.524 AC: 21731 AN: 41450

American (AMR) AF: 0.387 AC: 5898 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1812 AN: 3466

East Asian (EAS) AF: 0.200 AC: 1031 AN: 5152

South Asian (SAS) AF: 0.271 AC: 1305 AN: 4820

European-Finnish (FIN) AF: 0.513 AC: 5412 AN: 10556

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.506 AC: 34384 AN: 67964

Other (OTH) AF: 0.498 AC: 1053 AN: 2116

Alfa AF: 0.500 Hom.: 2398

Bravo AF: 0.473

Asia WGS AF: 0.272 AC: 946 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.7
DANN	Benign	0.58
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10977865; hg19: chr9-9603122;