chr9-9144115-A-T

Variant names:

• chr9-9144115-A-T
• rs10977527
• NM_002839.4:c.-143+39189T>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.-143+39189T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,182 control chromosomes in the GnomAD database, including 4,139 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 0.23 (4139 hom., cov: 33)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35
• Publications: 2 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRD	NM_002839.4	c.-143+39189T>A		intron_variant	Intron 10 of 45	ENST00000381196.9	NP_002830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRD	ENST00000381196.9	c.-143+39189T>A		intron_variant	Intron 10 of 45	5	NM_002839.4	ENSP00000370593.3
PTPRD	ENST00000463477.5	c.-143+39189T>A		intron_variant	Intron 11 of 16	1		ENSP00000417661.1
PTPRD	ENST00000850942.1	c.-143+39189T>A		intron_variant	Intron 12 of 47			ENSP00000521027.1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34773 AN: 152064 Hom.: 4143 Cov.: 33

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.229 AC: 34782 AN: 152182 Hom.: 4139 Cov.: 33 AF XY: 0.234 AC XY: 17381 AN XY: 74400

African (AFR) AF: 0.173 AC: 7177 AN: 41540

American (AMR) AF: 0.296 AC: 4531 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 880 AN: 3470

East Asian (EAS) AF: 0.245 AC: 1267 AN: 5168

South Asian (SAS) AF: 0.319 AC: 1541 AN: 4830

European-Finnish (FIN) AF: 0.244 AC: 2581 AN: 10592

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16082 AN: 67976

Other (OTH) AF: 0.226 AC: 476 AN: 2110

Alfa AF: 0.229 Hom.: 497

Bravo AF: 0.228

Asia WGS AF: 0.228 AC: 792 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.1
DANN	Benign	0.46
PhyloP100		1.3
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: rs10977527; hg19: chr9-9144115; COSMIC: COSV67063650;