1-214395560-C-T

Variant names:

• chr1-214395560-C-T
• rs4311855
• NM_005401.5:c.759-574G>A

Variant summary

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

The NM_005401.5(PTPN14):​c.759-574G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 150,120 control chromosomes in the GnomAD database, including 51,085 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 0.82 (51085 hom., cov: 25)
• Consequence: PTPN14 NM_005401.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0990
• Publications: 1 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005401.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN14	NM_005401.5	MANE Select	c.759-574G>A		intron	N/A	NP_005392.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN14	ENST00000366956.10	TSL:1 MANE Select	c.759-574G>A		intron	N/A	ENSP00000355923.4
	PTPN14	ENST00000543945.5	TSL:5	c.*35-574G>A		intron	N/A	ENSP00000443330.1

Frequencies

GnomAD3 genomes AF: 0.820 AC: 122942 AN: 150004 Hom.: 51024 Cov.: 25

Gnomad AFR AF: 0.961

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.725

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.777

Gnomad MID AF: 0.704

Gnomad NFE AF: 0.787

Gnomad OTH AF: 0.776

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

GnomAD4 genome AF: 0.820 AC: 123061 AN: 150120 Hom.: 51085 Cov.: 25 AF XY: 0.813 AC XY: 59470 AN XY: 73164

African (AFR) AF: 0.961 AC: 39169 AN: 40772

American (AMR) AF: 0.725 AC: 10910 AN: 15054

Ashkenazi Jewish (ASJ) AF: 0.732 AC: 2534 AN: 3462

East Asian (EAS) AF: 0.647 AC: 3217 AN: 4970

South Asian (SAS) AF: 0.765 AC: 3587 AN: 4690

European-Finnish (FIN) AF: 0.777 AC: 7888 AN: 10150

Middle Eastern (MID) AF: 0.719 AC: 210 AN: 292

European-Non Finnish (NFE) AF: 0.787 AC: 53299 AN: 67742

Other (OTH) AF: 0.777 AC: 1620 AN: 2084

Alfa AF: 0.811 Hom.: 12965

Bravo AF: 0.817

Asia WGS AF: 0.757 AC: 2627 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.73
DANN	Benign	0.14
PhyloP100		0.099
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: rs4311855; hg19: chr1-214568903;