rs2295136

chr14-88468358-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007039.4(PTPN21):c.3397-93C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 1,279,722 control chromosomes in the GnomAD database, including 96,200 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 0.35 (9858 hom., cov: 32)
  • Exomes 𝑓: 0.39 (86342 hom.)
• Consequence: PTPN21 NM_007039.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.744

Genes affected

PTPN21 (HGNC:9651): (protein tyrosine phosphatase non-receptor type 21) 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 N-terminal domain, similar to cytoskeletal- associated proteins including band 4.1, ezrin, merlin, and radixin. This PTP was shown to specially interact with BMX/ETK, a member of Tec tyrosine kinase family characterized by a multimodular structures including PH, SH3, and SH2 domains. The interaction of this PTP with BMX kinase was found to increase the activation of STAT3, but not STAT2 kinase. Studies of the similar gene in mice suggested the possible roles of this PTP in liver regeneration and spermatogenesis. [provided by RefSeq, Jul 2008]

SPATA7 (HGNC:20423): (spermatogenesis associated 7) This gene, originally isolated from testis, is also expressed in retina. Mutations in this gene are associated with Leber congenital amaurosis and juvenile retinitis pigmentosa. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN21	NM_007039.4	c.3397-93C>T		intron_variant		ENST00000556564.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN21	ENST00000556564.6	c.3397-93C>T		intron_variant		1	NM_007039.4	P1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53452 AN: 151948 Hom.: 9863 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.377

GnomAD4 exome AF: 0.387 AC: 436002 AN: 1127656 Hom.: 86342 AF XY: 0.384 AC XY: 215757 AN XY: 561632

Gnomad4 AFR exome AF: 0.303

Gnomad4 AMR exome AF: 0.200

Gnomad4 ASJ exome AF: 0.476

Gnomad4 EAS exome AF: 0.175

Gnomad4 SAS exome AF: 0.264

Gnomad4 FIN exome AF: 0.382

Gnomad4 NFE exome AF: 0.410

Gnomad4 OTH exome AF: 0.384

GnomAD4 genome AF: 0.352 AC: 53452 AN: 152066 Hom.: 9858 Cov.: 32 AF XY: 0.346 AC XY: 25725 AN XY: 74338

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.467

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.406

Gnomad4 OTH AF: 0.373

Alfa AF: 0.388 Hom.: 16342

Bravo AF: 0.341

Asia WGS AF: 0.213 AC: 743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	7.3
Dann	Benign	0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs2295136; hg19: chr14-88934702; COSMIC: COSV60846311; COSMIC: COSV60846311;