9-9951874-A-G

Variant names:

• chr9-9951874-A-G
• rs10978130
• NM_002839.4:c.-471-13264T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002839.4(PTPRD):​c.-471-13264T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0542 in 152,292 control chromosomes in the GnomAD database, including 392 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 0.054 (392 hom., cov: 32)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.858
• 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 (EAS) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRD	NM_002839.4	c.-471-13264T>C		intron_variant	Intron 4 of 45	ENST00000381196.9	NP_002830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRD	ENST00000381196.9	c.-471-13264T>C		intron_variant	Intron 4 of 45	5	NM_002839.4	ENSP00000370593.3
PTPRD	ENST00000463477.5	c.-543-13264T>C		intron_variant	Intron 4 of 16	1		ENSP00000417661.1
PTPRD	ENST00000850942.1	c.-471-13264T>C		intron_variant	Intron 6 of 47			ENSP00000521027.1

Frequencies

GnomAD3 genomes AF: 0.0542 AC: 8249 AN: 152174 Hom.: 393 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0289

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.0166

Gnomad FIN AF: 0.0215

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0258

Gnomad OTH AF: 0.0435

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

GnomAD4 genome AF: 0.0542 AC: 8259 AN: 152292 Hom.: 392 Cov.: 32 AF XY: 0.0537 AC XY: 3996 AN XY: 74474

African (AFR) AF: 0.115 AC: 4782 AN: 41548

American (AMR) AF: 0.0289 AC: 442 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0150 AC: 52 AN: 3468

East Asian (EAS) AF: 0.159 AC: 823 AN: 5178

South Asian (SAS) AF: 0.0166 AC: 80 AN: 4826

European-Finnish (FIN) AF: 0.0215 AC: 228 AN: 10624

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0258 AC: 1756 AN: 68032

Other (OTH) AF: 0.0430 AC: 91 AN: 2114

Alfa AF: 0.0353 Hom.: 631

Bravo AF: 0.0592

Asia WGS AF: 0.0680 AC: 236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.17
DANN	Benign	0.43
PhyloP100		-0.86
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: rs10978130; hg19: chr9-9951874;