14-88468307-G-A

Variant names:

• chr14-88468307-G-A
• rs366476
• NM_007039.4:c.3397-42C>T

Variant summary

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

The NM_007039.4(PTPN21):​c.3397-42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 1,538,546 control chromosomes in the GnomAD database, including 146,574 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 0.44 (15047 hom., cov: 32)
  • Exomes 𝑓: 0.43 (131527 hom.)
• Consequence: PTPN21 NM_007039.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 9 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]

SPATA7 (HGNC:20423): (spermatogenesis associated 7) This gene, originally isolated from testis, is also expressed in retina. Mutations in this gene are associated with Leber congenital amaurosis and juvenile retinitis pigmentosa. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

SPATA7 Gene-Disease associations (from GenCC):

• Leber congenital amaurosis 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Leber congenital amaurosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• severe early-childhood-onset retinal dystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN21	NM_007039.4	c.3397-42C>T		intron_variant	Intron 18 of 18	ENST00000556564.6	NP_008970.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN21	ENST00000556564.6	c.3397-42C>T		intron_variant	Intron 18 of 18	1	NM_007039.4	ENSP00000452414.1

Frequencies

GnomAD3 genomes AF: 0.441 AC: 66971 AN: 151848 Hom.: 15022 Cov.: 32

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.405

GnomAD2 exomes AF: 0.471 AC: 101216 AN: 215122 AF XY: 0.465

Gnomad AFR exome AF: 0.440

Gnomad AMR exome AF: 0.630

Gnomad ASJ exome AF: 0.362

Gnomad EAS exome AF: 0.590

Gnomad FIN exome AF: 0.488

Gnomad NFE exome AF: 0.420

Gnomad OTH exome AF: 0.449

GnomAD4 exome AF: 0.431 AC: 598031 AN: 1386580 Hom.: 131527 Cov.: 31 AF XY: 0.432 AC XY: 297234 AN XY: 688206

African (AFR) AF: 0.428 AC: 12985 AN: 30354

American (AMR) AF: 0.610 AC: 20669 AN: 33878

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 8402 AN: 24068

East Asian (EAS) AF: 0.649 AC: 25051 AN: 38614

South Asian (SAS) AF: 0.476 AC: 37070 AN: 77936

European-Finnish (FIN) AF: 0.481 AC: 24911 AN: 51746

Middle Eastern (MID) AF: 0.347 AC: 1390 AN: 4002

European-Non Finnish (NFE) AF: 0.414 AC: 442874 AN: 1068746

Other (OTH) AF: 0.431 AC: 24679 AN: 57236

GnomAD4 genome AF: 0.441 AC: 67049 AN: 151966 Hom.: 15047 Cov.: 32 AF XY: 0.448 AC XY: 33273 AN XY: 74270

African (AFR) AF: 0.434 AC: 17988 AN: 41434

American (AMR) AF: 0.528 AC: 8065 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1213 AN: 3472

East Asian (EAS) AF: 0.585 AC: 3012 AN: 5152

South Asian (SAS) AF: 0.458 AC: 2204 AN: 4810

European-Finnish (FIN) AF: 0.478 AC: 5043 AN: 10546

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28143 AN: 67966

Other (OTH) AF: 0.412 AC: 868 AN: 2106

Alfa AF: 0.424 Hom.: 27250

Bravo AF: 0.447

Asia WGS AF: 0.545 AC: 1897 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.043
DANN	Benign	0.73
PhyloP100		-1.4
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: rs366476; hg19: chr14-88934651;