9-8416196-T-C

Variant names:

• chr9-8416196-T-C
• rs10511494
• NM_002839.4:c.4087-11536A>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.4087-11536A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,136 control chromosomes in the GnomAD database, including 2,703 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 0.18 (2703 hom., cov: 32)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 5 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002839.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRD	NM_002839.4	MANE Select	c.4087-11536A>G		intron	N/A	NP_002830.1	P23468-1
	PTPRD	NM_001377958.1		c.4147-11536A>G		intron	N/A	NP_001364887.1
	PTPRD	NM_001378058.1		c.4102-11536A>G		intron	N/A	NP_001364987.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRD	ENST00000381196.9	TSL:5 MANE Select	c.4087-11536A>G		intron	N/A	ENSP00000370593.3	P23468-1
	PTPRD	ENST00000355233.9	TSL:1	c.2869-11536A>G		intron	N/A	ENSP00000347373.5	P23468-6
	PTPRD	ENST00000397606.7	TSL:1	c.2866-11536A>G		intron	N/A	ENSP00000380731.3	P23468-4

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26626 AN: 152018 Hom.: 2701 Cov.: 32

Gnomad AFR AF: 0.0929

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.0572

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.175 AC: 26637 AN: 152136 Hom.: 2703 Cov.: 32 AF XY: 0.177 AC XY: 13123 AN XY: 74326

African (AFR) AF: 0.0931 AC: 3868 AN: 41546

American (AMR) AF: 0.142 AC: 2169 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 613 AN: 3472

East Asian (EAS) AF: 0.0571 AC: 296 AN: 5182

South Asian (SAS) AF: 0.101 AC: 487 AN: 4816

European-Finnish (FIN) AF: 0.287 AC: 3022 AN: 10536

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15367 AN: 67992

Other (OTH) AF: 0.182 AC: 385 AN: 2114

Alfa AF: 0.208 Hom.: 13941

Bravo AF: 0.161

Asia WGS AF: 0.0710 AC: 247 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.14
DANN	Benign	0.46
PhyloP100		-1.2
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10511494;

hg19: chr9-8416196;