rs11847417

Variant names:

• chr14-88510606-C-T
• rs11847417
• NM_007039.4:c.351-2586G>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.351-2586G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 151,922 control chromosomes in the GnomAD database, including 9,748 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 (9748 hom., cov: 32)
• Consequence: PTPN21 NM_007039.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.256
• Publications: 6 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 (AFR) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN21	NM_007039.4	c.351-2586G>A		intron_variant	Intron 3 of 18	ENST00000556564.6	NP_008970.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN21	ENST00000556564.6	c.351-2586G>A		intron_variant	Intron 3 of 18	1	NM_007039.4	ENSP00000452414.1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52686 AN: 151804 Hom.: 9717 Cov.: 32

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.347 AC: 52783 AN: 151922 Hom.: 9748 Cov.: 32 AF XY: 0.343 AC XY: 25451 AN XY: 74252

African (AFR) AF: 0.480 AC: 19879 AN: 41422

American (AMR) AF: 0.247 AC: 3769 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1061 AN: 3472

East Asian (EAS) AF: 0.352 AC: 1814 AN: 5156

South Asian (SAS) AF: 0.345 AC: 1658 AN: 4808

European-Finnish (FIN) AF: 0.281 AC: 2963 AN: 10550

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.303 AC: 20592 AN: 67934

Other (OTH) AF: 0.315 AC: 665 AN: 2110

Alfa AF: 0.333 Hom.: 1520

Bravo AF: 0.349

Asia WGS AF: 0.347 AC: 1209 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	9.7
DANN	Benign	0.77
PhyloP100		0.26
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: rs11847417; hg19: chr14-88976950;