9-9539574-C-T

Variant names:

• chr9-9539574-C-T
• rs639168
• NM_002839.4:c.-237+35158G>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.-237+35158G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 151,702 control chromosomes in the GnomAD database, including 2,071 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 0.16 (2071 hom., cov: 32)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.257
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRD	NM_002839.4	c.-237+35158G>A		intron_variant	Intron 8 of 45	ENST00000381196.9	NP_002830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRD	ENST00000381196.9	c.-237+35158G>A		intron_variant	Intron 8 of 45	5	NM_002839.4	ENSP00000370593.3
PTPRD	ENST00000463477.5	c.-309+35158G>A		intron_variant	Intron 8 of 16	1		ENSP00000417661.1
PTPRD	ENST00000850942.1	c.-237+35158G>A		intron_variant	Intron 10 of 47			ENSP00000521027.1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24114 AN: 151582 Hom.: 2061 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.0835

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.159 AC: 24167 AN: 151702 Hom.: 2071 Cov.: 32 AF XY: 0.159 AC XY: 11766 AN XY: 74166

African (AFR) AF: 0.228 AC: 9433 AN: 41378

American (AMR) AF: 0.144 AC: 2186 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 355 AN: 3464

East Asian (EAS) AF: 0.172 AC: 880 AN: 5126

South Asian (SAS) AF: 0.0840 AC: 406 AN: 4834

European-Finnish (FIN) AF: 0.148 AC: 1567 AN: 10574

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8901 AN: 67828

Other (OTH) AF: 0.132 AC: 279 AN: 2106

Alfa AF: 0.150 Hom.: 430

Bravo AF: 0.161

Asia WGS AF: 0.155 AC: 540 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.3
DANN	Benign	0.64
PhyloP100		-0.26
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: rs639168; hg19: chr9-9539574; COSMIC: COSV67006046;