rs11120313

Variant names:

• chr1-214407863-C-A
• rs11120313
• NM_005401.5:c.510+3821G>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.510+3821G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,164 control chromosomes in the GnomAD database, including 1,075 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 0.11 (1075 hom., cov: 32)
• Consequence: PTPN14 NM_005401.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 2 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN14	NM_005401.5	c.510+3821G>T		intron_variant	Intron 5 of 18	ENST00000366956.10	NP_005392.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN14	ENST00000366956.10	c.510+3821G>T		intron_variant	Intron 5 of 18	1	NM_005401.5	ENSP00000355923.4
PTPN14	ENST00000543945.5	c.510+3821G>T		intron_variant	Intron 5 of 17	5		ENSP00000443330.1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 16973 AN: 152046 Hom.: 1070 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0689

Gnomad EAS AF: 0.00847

Gnomad SAS AF: 0.0782

Gnomad FIN AF: 0.0639

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0950

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.112 AC: 16986 AN: 152164 Hom.: 1075 Cov.: 32 AF XY: 0.110 AC XY: 8197 AN XY: 74412

African (AFR) AF: 0.169 AC: 7013 AN: 41464

American (AMR) AF: 0.114 AC: 1741 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0689 AC: 239 AN: 3470

East Asian (EAS) AF: 0.00811 AC: 42 AN: 5180

South Asian (SAS) AF: 0.0778 AC: 375 AN: 4820

European-Finnish (FIN) AF: 0.0639 AC: 678 AN: 10604

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.0951 AC: 6465 AN: 68012

Other (OTH) AF: 0.125 AC: 264 AN: 2114

Alfa AF: 0.103 Hom.: 2306

Bravo AF: 0.121

Asia WGS AF: 0.0590 AC: 207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.15
DANN	Benign	0.62
PhyloP100		-1.2
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: rs11120313; hg19: chr1-214581206; COSMIC: COSV65282421;