rs12757404

Positions:

• chr1-214456273-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005401.5(PTPN14):​c.175-4299T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 152,058 control chromosomes in the GnomAD database, including 11,274 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 0.38 (11274 hom., cov: 33)
• Consequence: PTPN14 NM_005401.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.811

Genes affected

PTPN14 (HGNC:9647): (protein tyrosine phosphatase non-receptor type 14) 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 noncatalytic domain similar to that of band 4.1 superfamily cytoskeleton-associated proteins, which suggested the membrane or cytoskeleton localization of this protein. It appears to regulate lymphatic development in mammals, and a loss of function mutation has been found in a kindred with a lymphedema-choanal atresia. [provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN14	NM_005401.5	c.175-4299T>C		intron_variant		ENST00000366956.10	NP_005392.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN14	ENST00000366956.10	c.175-4299T>C		intron_variant		1	NM_005401.5	ENSP00000355923	P1
PTPN14	ENST00000543945.5	c.175-4299T>C		intron_variant		5		ENSP00000443330

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57747 AN: 151940 Hom.: 11269 Cov.: 33

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.380 AC: 57787 AN: 152058 Hom.: 11274 Cov.: 33 AF XY: 0.379 AC XY: 28182 AN XY: 74332

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.542

Gnomad4 EAS AF: 0.526

Gnomad4 SAS AF: 0.390

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.396

Gnomad4 OTH AF: 0.420

Alfa AF: 0.407 Hom.: 20842

Bravo AF: 0.393

Asia WGS AF: 0.401 AC: 1396 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.7
DANN	Benign	0.59

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: rs12757404; hg19: chr1-214629616;