rs10150311

Variant names:

• chr14-88510128-T-C
• rs10150311
• NM_007039.4:c.351-2108A>G

Variant summary

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

The NM_007039.4(PTPN21):​c.351-2108A>G 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 152,082 control chromosomes in the GnomAD database, including 9,729 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 (9729 hom., cov: 32)
• Consequence: PTPN21 NM_007039.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007039.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN21	NM_007039.4	MANE Select	c.351-2108A>G		intron	N/A	NP_008970.2	Q16825

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN21	ENST00000556564.6	TSL:1 MANE Select	c.351-2108A>G		intron	N/A	ENSP00000452414.1	Q16825
	PTPN21	ENST00000328736.7	TSL:1	c.351-2108A>G		intron	N/A	ENSP00000330276.3	Q16825
	PTPN21	ENST00000536337.5	TSL:1	n.*288-2108A>G		intron	N/A	ENSP00000443951.1	G3V1Q9

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52666 AN: 151964 Hom.: 9698 Cov.: 32

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.204

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: 52763 AN: 152082 Hom.: 9729 Cov.: 32 AF XY: 0.342 AC XY: 25443 AN XY: 74340

African (AFR) AF: 0.479 AC: 19858 AN: 41474

American (AMR) AF: 0.247 AC: 3774 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1058 AN: 3466

East Asian (EAS) AF: 0.352 AC: 1822 AN: 5182

South Asian (SAS) AF: 0.345 AC: 1664 AN: 4822

European-Finnish (FIN) AF: 0.280 AC: 2955 AN: 10572

Middle Eastern (MID) AF: 0.212 AC: 62 AN: 292

European-Non Finnish (NFE) AF: 0.303 AC: 20584 AN: 67960

Other (OTH) AF: 0.315 AC: 666 AN: 2116

Alfa AF: 0.334 Hom.: 2418

Bravo AF: 0.349

Asia WGS AF: 0.347 AC: 1209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.5
DANN	Benign	0.87
PhyloP100		1.1
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: rs10150311; hg19: chr14-88976472;