rs322323

Variant names:

• chr7-137255813-T-C
• rs322323
• NM_002825.7:c.-1-839A>G

Variant summary

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

The NM_002825.7(PTN):​c.-1-839A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 152,018 control chromosomes in the GnomAD database, including 15,018 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 0.44 (15018 hom., cov: 32)
• Consequence: PTN NM_002825.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454
• Publications: 1 publications found

Genes affected

PTN (HGNC:9630): (pleiotrophin) The protein encoded by this gene is a secreted heparin-binding growth factor. The protein has significant roles in cell growth and survival, cell migration, angiogenesis and tumorigenesis. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Oct 2016]

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 (AFR) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTN	NM_002825.7	c.-1-839A>G		intron_variant	Intron 1 of 4	ENST00000348225.7	NP_002816.1
PTN	NM_001321386.2	c.-1-839A>G		intron_variant	Intron 1 of 4		NP_001308315.1
PTN	NM_001321387.3	c.-1-839A>G		intron_variant	Intron 1 of 4		NP_001308316.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTN	ENST00000348225.7	c.-1-839A>G		intron_variant	Intron 1 of 4	1	NM_002825.7	ENSP00000341170.2
PTN	ENST00000699293.1	c.-1-839A>G		intron_variant	Intron 1 of 4			ENSP00000514273.1
PTN	ENST00000393083.2	c.-1-839A>G		intron_variant	Intron 1 of 5	5		ENSP00000376798.2

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66893 AN: 151902 Hom.: 14984 Cov.: 32

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.458

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.431

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

GnomAD4 genome AF: 0.440 AC: 66961 AN: 152018 Hom.: 15018 Cov.: 32 AF XY: 0.440 AC XY: 32704 AN XY: 74314

African (AFR) AF: 0.526 AC: 21825 AN: 41458

American (AMR) AF: 0.389 AC: 5931 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 1777 AN: 3464

East Asian (EAS) AF: 0.349 AC: 1803 AN: 5164

South Asian (SAS) AF: 0.439 AC: 2118 AN: 4820

European-Finnish (FIN) AF: 0.415 AC: 4387 AN: 10574

Middle Eastern (MID) AF: 0.459 AC: 133 AN: 290

European-Non Finnish (NFE) AF: 0.410 AC: 27859 AN: 67976

Other (OTH) AF: 0.428 AC: 904 AN: 2110

Alfa AF: 0.437 Hom.: 17127

Bravo AF: 0.441

Asia WGS AF: 0.399 AC: 1391 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	2.1
DANN	Benign	0.66
PhyloP100		-0.45
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: rs322323; hg19: chr7-136940560;