rs1998670

Variant names:

• chr14-88504581-C-T
• rs1998670
• NM_007039.4:c.517-86G>A

Variant summary

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

The NM_007039.4(PTPN21):​c.517-86G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,090,820 control chromosomes in the GnomAD database, including 34,188 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 0.23 (4230 hom., cov: 32)
  • Exomes 𝑓: 0.25 (29958 hom.)
• Consequence: PTPN21 NM_007039.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.957
• Publications: 8 publications found

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]

ENSG00000258983 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN21	NM_007039.4	c.517-86G>A		intron_variant	Intron 5 of 18	ENST00000556564.6	NP_008970.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN21	ENST00000556564.6	c.517-86G>A		intron_variant	Intron 5 of 18	1	NM_007039.4	ENSP00000452414.1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35191 AN: 151772 Hom.: 4222 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.247 AC: 232223 AN: 938930 Hom.: 29958 AF XY: 0.247 AC XY: 120209 AN XY: 487450

African (AFR) AF: 0.182 AC: 4188 AN: 23042

American (AMR) AF: 0.186 AC: 7761 AN: 41618

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 4856 AN: 22302

East Asian (EAS) AF: 0.290 AC: 10616 AN: 36576

South Asian (SAS) AF: 0.217 AC: 15518 AN: 71492

European-Finnish (FIN) AF: 0.241 AC: 12497 AN: 51832

Middle Eastern (MID) AF: 0.119 AC: 558 AN: 4706

European-Non Finnish (NFE) AF: 0.257 AC: 165763 AN: 644450

Other (OTH) AF: 0.244 AC: 10466 AN: 42912

GnomAD4 genome AF: 0.232 AC: 35231 AN: 151890 Hom.: 4230 Cov.: 32 AF XY: 0.229 AC XY: 16988 AN XY: 74208

African (AFR) AF: 0.184 AC: 7610 AN: 41412

American (AMR) AF: 0.198 AC: 3024 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 765 AN: 3472

East Asian (EAS) AF: 0.317 AC: 1632 AN: 5144

South Asian (SAS) AF: 0.245 AC: 1180 AN: 4814

European-Finnish (FIN) AF: 0.242 AC: 2541 AN: 10502

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.261 AC: 17712 AN: 67964

Other (OTH) AF: 0.209 AC: 439 AN: 2104

Alfa AF: 0.253 Hom.: 2610

Bravo AF: 0.226

Asia WGS AF: 0.256 AC: 890 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	0.18
DANN	Benign	0.48
PhyloP100		-0.96
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: rs1998670; hg19: chr14-88970925; COSMIC: COSV60848401;