rs6656559

Variant names:

• chr1-214453240-T-A
• rs6656559
• NM_005401.5:c.175-1266A>T

Variant summary

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

The NM_005401.5(PTPN14):​c.175-1266A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,198 control chromosomes in the GnomAD database, including 6,845 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 0.28 (6845 hom., cov: 33)
• Consequence: PTPN14 NM_005401.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 3 publications found

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]

PTPN14 Gene-Disease associations (from GenCC):

• lymphedema-posterior choanal atresia syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN14	NM_005401.5	c.175-1266A>T		intron_variant	Intron 2 of 18	ENST00000366956.10	NP_005392.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN14	ENST00000366956.10	c.175-1266A>T		intron_variant	Intron 2 of 18	1	NM_005401.5	ENSP00000355923.4
PTPN14	ENST00000543945.5	c.175-1266A>T		intron_variant	Intron 2 of 17	5		ENSP00000443330.1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42173 AN: 152080 Hom.: 6844 Cov.: 33

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.277 AC: 42179 AN: 152198 Hom.: 6845 Cov.: 33 AF XY: 0.279 AC XY: 20725 AN XY: 74402

African (AFR) AF: 0.115 AC: 4797 AN: 41564

American (AMR) AF: 0.297 AC: 4538 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 716 AN: 3470

East Asian (EAS) AF: 0.157 AC: 815 AN: 5186

South Asian (SAS) AF: 0.233 AC: 1126 AN: 4824

European-Finnish (FIN) AF: 0.418 AC: 4414 AN: 10568

Middle Eastern (MID) AF: 0.281 AC: 82 AN: 292

European-Non Finnish (NFE) AF: 0.363 AC: 24688 AN: 67992

Other (OTH) AF: 0.278 AC: 587 AN: 2112

Alfa AF: 0.312 Hom.: 1021

Bravo AF: 0.261

Asia WGS AF: 0.241 AC: 838 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.65
DANN	Benign	0.72
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs6656559; hg19: chr1-214626583; COSMIC: COSV65282520;