rs10138002

Positions:

• chr14-88510071-C-T

Variant summary

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

The NM_007039.4(PTPN21):​c.351-2051G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 151,948 control chromosomes in the GnomAD database, including 9,336 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 0.34 (9336 hom., cov: 32)
• Consequence: PTPN21 NM_007039.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.658

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN21	NM_007039.4	c.351-2051G>A		intron_variant		ENST00000556564.6	NP_008970.2
LOC105370614	XR_007064296.1	n.166-3839C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN21	ENST00000556564.6	c.351-2051G>A		intron_variant		1	NM_007039.4	ENSP00000452414	P1
	ENST00000555444.2	n.316-3839C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51824 AN: 151832 Hom.: 9306 Cov.: 32

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.342 AC: 51916 AN: 151948 Hom.: 9336 Cov.: 32 AF XY: 0.337 AC XY: 25065 AN XY: 74292

Gnomad4 AFR AF: 0.460

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.352

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.280

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.313

Alfa AF: 0.302 Hom.: 11630

Bravo AF: 0.343

Asia WGS AF: 0.348 AC: 1210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.3
DANN	Benign	0.43

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: rs10138002; hg19: chr14-88976415;