14-88479169-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_007039.4(PTPN21):c.2262C>T(p.Pro754=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 1,551,738 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (12 hom., cov: 32)
  • Exomes 𝑓: 0.00093 (17 hom.)
• Consequence: PTPN21 NM_007039.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0170

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 14-88479169-G-A is Benign according to our data. Variant chr14-88479169-G-A is described in ClinVar as [Benign]. Clinvar id is 768671.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.017 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0101 (1541/152300) while in subpopulation AFR AF= 0.0354 (1471/41568). AF 95% confidence interval is 0.0339. There are 12 homozygotes in gnomad4. There are 705 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN21	NM_007039.4	c.2262C>T	p.Pro754=	synonymous_variant	13/19	ENST00000556564.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN21	ENST00000556564.6	c.2262C>T	p.Pro754=	synonymous_variant	13/19	1	NM_007039.4	P1
PTPN21	ENST00000328736.7	c.2262C>T	p.Pro754=	synonymous_variant	12/18	1		P1
PTPN21	ENST00000554270.5	n.2375C>T		non_coding_transcript_exon_variant	12/17	1
PTPN21	ENST00000536337.5	c.*2199C>T		3_prime_UTR_variant, NMD_transcript_variant	13/19	1

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1534 AN: 152182 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0353

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00286 AC: 550 AN: 192368 Hom.: 4 AF XY: 0.00214 AC XY: 222 AN XY: 103918

Gnomad AFR exome AF: 0.0360

Gnomad AMR exome AF: 0.00130

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000617

Gnomad SAS exome AF: 0.0000525

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000332

Gnomad OTH exome AF: 0.000889

GnomAD4 exome AF: 0.000933 AC: 1305 AN: 1399438 Hom.: 17 Cov.: 31 AF XY: 0.000828 AC XY: 572 AN XY: 691102

Gnomad4 AFR exome AF: 0.0353

Gnomad4 AMR exome AF: 0.00160

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000926

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000360

Gnomad4 OTH exome AF: 0.00187

GnomAD4 genome AF: 0.0101 AC: 1541 AN: 152300 Hom.: 12 Cov.: 32 AF XY: 0.00947 AC XY: 705 AN XY: 74460

Gnomad4 AFR AF: 0.0354

Gnomad4 AMR AF: 0.00314

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00493 Hom.: 3

Bravo AF: 0.0113

Asia WGS AF: 0.00202 AC: 8 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 04, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	0.063
Dann	Benign	0.74

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: rs61747078; hg19: chr14-88945513;