9-9770495-C-T

Variant names:

• chr9-9770495-C-T
• rs768224
• NM_002839.4:c.-367-3644G>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.-367-3644G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 151,834 control chromosomes in the GnomAD database, including 16,099 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 0.45 (16099 hom., cov: 32)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRD	NM_002839.4	c.-367-3644G>A		intron_variant	Intron 5 of 45	ENST00000381196.9	NP_002830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRD	ENST00000381196.9	c.-367-3644G>A		intron_variant	Intron 5 of 45	5	NM_002839.4	ENSP00000370593.3
PTPRD	ENST00000463477.5	c.-439-3644G>A		intron_variant	Intron 5 of 16	1		ENSP00000417661.1
PTPRD	ENST00000850942.1	c.-367-3644G>A		intron_variant	Intron 7 of 47			ENSP00000521027.1

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68874 AN: 151716 Hom.: 16058 Cov.: 32

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.454 AC: 68966 AN: 151834 Hom.: 16099 Cov.: 32 AF XY: 0.462 AC XY: 34252 AN XY: 74204

African (AFR) AF: 0.519 AC: 21497 AN: 41388

American (AMR) AF: 0.468 AC: 7149 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1206 AN: 3470

East Asian (EAS) AF: 0.693 AC: 3581 AN: 5168

South Asian (SAS) AF: 0.521 AC: 2508 AN: 4818

European-Finnish (FIN) AF: 0.477 AC: 5020 AN: 10518

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26738 AN: 67900

Other (OTH) AF: 0.422 AC: 888 AN: 2104

Alfa AF: 0.424 Hom.: 1767

Bravo AF: 0.456

Asia WGS AF: 0.643 AC: 2229 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.83
DANN	Benign	0.32
PhyloP100		-0.21
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: rs768224; hg19: chr9-9770495; COSMIC: COSV67006136;