14-88484662-C-G

Variant names:

• chr14-88484662-C-G
• rs1864744
• NM_007039.4:c.1078+414G>C

Variant summary

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

The NM_007039.4(PTPN21):​c.1078+414G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 151,934 control chromosomes in the GnomAD database, including 11,176 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 0.37 (11176 hom., cov: 32)
• Consequence: PTPN21 NM_007039.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505
• Publications: 14 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN21	NM_007039.4	c.1078+414G>C		intron_variant	Intron 12 of 18	ENST00000556564.6	NP_008970.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN21	ENST00000556564.6	c.1078+414G>C		intron_variant	Intron 12 of 18	1	NM_007039.4	ENSP00000452414.1
PTPN21	ENST00000328736.7	c.1078+414G>C		intron_variant	Intron 11 of 17	1		ENSP00000330276.3
PTPN21	ENST00000536337.5	n.*1015+414G>C		intron_variant	Intron 12 of 18	1		ENSP00000443951.1
PTPN21	ENST00000554270.5	n.1191+414G>C		intron_variant	Intron 11 of 16	1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56714 AN: 151818 Hom.: 11153 Cov.: 32

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.374 AC: 56807 AN: 151934 Hom.: 11176 Cov.: 32 AF XY: 0.368 AC XY: 27326 AN XY: 74240

African (AFR) AF: 0.496 AC: 20544 AN: 41416

American (AMR) AF: 0.272 AC: 4146 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1137 AN: 3466

East Asian (EAS) AF: 0.343 AC: 1769 AN: 5160

South Asian (SAS) AF: 0.420 AC: 2022 AN: 4820

European-Finnish (FIN) AF: 0.283 AC: 2983 AN: 10534

Middle Eastern (MID) AF: 0.269 AC: 78 AN: 290

European-Non Finnish (NFE) AF: 0.340 AC: 23080 AN: 67962

Other (OTH) AF: 0.336 AC: 709 AN: 2112

Alfa AF: 0.222 Hom.: 486

Bravo AF: 0.376

Asia WGS AF: 0.390 AC: 1356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.20
PhyloP100		-0.51
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: rs1864744; hg19: chr14-88951006;