chr9-10043014-T-G

Variant names:

• chr9-10043014-T-G
• rs291272
• NM_002839.4:c.-544-9224A>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.-544-9224A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0925 in 151,922 control chromosomes in the GnomAD database, including 1,310 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 0.093 (1310 hom., cov: 32)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.745
• 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=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.226 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.-544-9224A>C		intron	N/A	NP_002830.1	P23468-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRD	ENST00000381196.9	TSL:5 MANE Select	c.-544-9224A>C		intron	N/A	ENSP00000370593.3	P23468-1
	PTPRD	ENST00000463477.5	TSL:1	c.-616-9224A>C		intron	N/A	ENSP00000417661.1	C9J8S8
	PTPRD	ENST00000850942.1		c.-544-9224A>C		intron	N/A	ENSP00000521027.1

Frequencies

GnomAD3 genomes AF: 0.0924 AC: 14020 AN: 151804 Hom.: 1307 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0302

Gnomad FIN AF: 0.0305

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0303

Gnomad OTH AF: 0.0729

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

GnomAD4 genome AF: 0.0925 AC: 14057 AN: 151922 Hom.: 1310 Cov.: 32 AF XY: 0.0908 AC XY: 6743 AN XY: 74276

African (AFR) AF: 0.229 AC: 9508 AN: 41440

American (AMR) AF: 0.118 AC: 1791 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 53 AN: 3466

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5172

South Asian (SAS) AF: 0.0309 AC: 149 AN: 4826

European-Finnish (FIN) AF: 0.0305 AC: 324 AN: 10608

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0303 AC: 2058 AN: 67902

Other (OTH) AF: 0.0722 AC: 152 AN: 2106

Alfa AF: 0.0471 Hom.: 1123

Bravo AF: 0.106

Asia WGS AF: 0.0260 AC: 90 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.87
PhyloP100		0.74
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: rs291272; hg19: chr9-10043014;