rs12323840

Positions:

• chr14-88541082-C-A

Variant summary

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

The NM_007039.4(PTPN21):​c.180+9156G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0607 in 152,104 control chromosomes in the GnomAD database, including 362 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 0.061 (362 hom., cov: 32)
• Consequence: PTPN21 NM_007039.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN21	NM_007039.4	c.180+9156G>T		intron_variant		ENST00000556564.6	NP_008970.2
PTPN21	XM_005267287.4	c.180+9156G>T		intron_variant			XP_005267344.1
PTPN21	XM_011536367.4	c.180+9156G>T		intron_variant			XP_011534669.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN21	ENST00000556564.6	c.180+9156G>T		intron_variant		1	NM_007039.4	ENSP00000452414	P1

Frequencies

GnomAD3 genomes AF: 0.0605 AC: 9196 AN: 151986 Hom.: 356 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.0364

Gnomad AMR AF: 0.0269

Gnomad ASJ AF: 0.0798

Gnomad EAS AF: 0.00926

Gnomad SAS AF: 0.0879

Gnomad FIN AF: 0.0388

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0417

Gnomad OTH AF: 0.0551

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

GnomAD4 genome AF: 0.0607 AC: 9231 AN: 152104 Hom.: 362 Cov.: 32 AF XY: 0.0613 AC XY: 4561 AN XY: 74374

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.0268

Gnomad4 ASJ AF: 0.0798

Gnomad4 EAS AF: 0.00948

Gnomad4 SAS AF: 0.0884

Gnomad4 FIN AF: 0.0388

Gnomad4 NFE AF: 0.0418

Gnomad4 OTH AF: 0.0621

Alfa AF: 0.0577 Hom.: 51

Bravo AF: 0.0592

Asia WGS AF: 0.0640 AC: 223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.45

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: rs12323840; hg19: chr14-89007426;