chr9-10174668-A-C

Variant names:

• chr9-10174668-A-C
• rs1358889
• NM_002839.4:c.-544-140878T>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.-544-140878T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 151,576 control chromosomes in the GnomAD database, including 4,019 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 (4019 hom., cov: 31)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRD	NM_002839.4	c.-544-140878T>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.-544-140878T>G		intron_variant	Intron 3 of 45	5	NM_002839.4	ENSP00000370593.3
PTPRD	ENST00000463477.5	c.-616-140878T>G		intron_variant	Intron 3 of 16	1		ENSP00000417661.1
PTPRD	ENST00000850942.1	c.-634+24754T>G		intron_variant	Intron 4 of 47			ENSP00000521027.1

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34761 AN: 151456 Hom.: 4019 Cov.: 31

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.230 AC: 34791 AN: 151576 Hom.: 4019 Cov.: 31 AF XY: 0.231 AC XY: 17134 AN XY: 74060

African (AFR) AF: 0.193 AC: 7989 AN: 41306

American (AMR) AF: 0.217 AC: 3293 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 838 AN: 3464

East Asian (EAS) AF: 0.225 AC: 1160 AN: 5146

South Asian (SAS) AF: 0.281 AC: 1346 AN: 4796

European-Finnish (FIN) AF: 0.274 AC: 2880 AN: 10516

Middle Eastern (MID) AF: 0.312 AC: 91 AN: 292

European-Non Finnish (NFE) AF: 0.242 AC: 16417 AN: 67850

Other (OTH) AF: 0.243 AC: 509 AN: 2096

Alfa AF: 0.239 Hom.: 2613

Bravo AF: 0.224

Asia WGS AF: 0.253 AC: 879 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.47
DANN	Benign	0.34
PhyloP100		0.19
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: rs1358889; hg19: chr9-10174668;