9-9015087-T-C

Variant names:

• chr9-9015087-T-C
• rs78925264
• NM_002839.4:c.-104+3610A>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.-104+3610A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0304 in 152,250 control chromosomes in the GnomAD database, including 75 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 0.030 (75 hom., cov: 32)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.279
• Publications: 3 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 (EAS) allele frequency at 95% confidence interval = 0.0541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRD	NM_002839.4	c.-104+3610A>G		intron_variant	Intron 11 of 45	ENST00000381196.9	NP_002830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRD	ENST00000381196.9	c.-104+3610A>G		intron_variant	Intron 11 of 45	5	NM_002839.4	ENSP00000370593.3
PTPRD	ENST00000463477.5	c.-104+3610A>G		intron_variant	Intron 12 of 16	1		ENSP00000417661.1
PTPRD	ENST00000850942.1	c.-104+3610A>G		intron_variant	Intron 13 of 47			ENSP00000521027.1

Frequencies

GnomAD3 genomes AF: 0.0304 AC: 4625 AN: 152132 Hom.: 76 Cov.: 32

Gnomad AFR AF: 0.0520

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0197

Gnomad ASJ AF: 0.00721

Gnomad EAS AF: 0.0596

Gnomad SAS AF: 0.0319

Gnomad FIN AF: 0.0445

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0169

Gnomad OTH AF: 0.0249

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

GnomAD4 genome AF: 0.0304 AC: 4625 AN: 152250 Hom.: 75 Cov.: 32 AF XY: 0.0313 AC XY: 2329 AN XY: 74446

African (AFR) AF: 0.0520 AC: 2159 AN: 41554

American (AMR) AF: 0.0197 AC: 301 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00721 AC: 25 AN: 3468

East Asian (EAS) AF: 0.0596 AC: 308 AN: 5172

South Asian (SAS) AF: 0.0313 AC: 151 AN: 4824

European-Finnish (FIN) AF: 0.0445 AC: 472 AN: 10610

Middle Eastern (MID) AF: 0.0205 AC: 6 AN: 292

European-Non Finnish (NFE) AF: 0.0169 AC: 1151 AN: 68032

Other (OTH) AF: 0.0247 AC: 52 AN: 2108

Alfa AF: 0.0195 Hom.: 14

Bravo AF: 0.0303

Asia WGS AF: 0.0470 AC: 163 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.92
DANN	Benign	0.76
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism

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: rs78925264; hg19: chr9-9015087;