Variant chr1-214369476-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005401.5(PTPN14):c.3252A>G(p.Glu1084=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 1,613,800 control chromosomes in the GnomAD database, including 498,283 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.81 ( 50200 hom., cov: 32)

Exomes 𝑓: 0.78 ( 448083 hom. )

Consequence

PTPN14
NM_005401.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0750

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 1-214369476-T-C is Benign according to our data. Variant chr1-214369476-T-C is described in ClinVar as [Benign]. Clinvar id is 1263765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-214369476-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.075 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN14	NM_005401.5 linkuse as main transcript	c.3252A>G	p.Glu1084=	synonymous_variant	17/19	ENST00000366956.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN14	ENST00000366956.10 linkuse as main transcript	c.3252A>G	p.Glu1084=	synonymous_variant	17/19	1	NM_005401.5	P1
PTPN14	ENST00000543945.5 linkuse as main transcript	c.*2528A>G		3_prime_UTR_variant	16/18	5

Frequencies

GnomAD3 genomes

AF:

0.807

AC:

122777

AN:

152050

Hom.:

50147

Cov.:

show subpopulations

Gnomad AFR

AF:

0.932

Gnomad AMI

AF:

0.705

Gnomad AMR

AF:

0.694

Gnomad ASJ

AF:

0.710

Gnomad EAS

AF:

0.633

Gnomad SAS

AF:

0.781

Gnomad FIN

AF:

0.783

Gnomad MID

AF:

0.690

Gnomad NFE

AF:

0.784

Gnomad OTH

AF:

0.762

GnomAD3 exomes

AF:

0.759

AC:

190876

AN:

251398

Hom.:

73352

AF XY:

0.760

AC XY:

103327

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.938

Gnomad AMR exome

AF:

0.649

Gnomad ASJ exome

AF:

0.708

Gnomad EAS exome

AF:

0.621

Gnomad SAS exome

AF:

0.779

Gnomad FIN exome

AF:

0.786

Gnomad NFE exome

AF:

0.784

Gnomad OTH exome

AF:

0.747

GnomAD4 exome

AF:

0.781

AC:

1142047

AN:

1461632

Hom.:

448083

Cov.:

AF XY:

0.780

AC XY:

567475

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.940

Gnomad4 AMR exome

AF:

0.652

Gnomad4 ASJ exome

AF:

0.710

Gnomad4 EAS exome

AF:

0.610

Gnomad4 SAS exome

AF:

0.781

Gnomad4 FIN exome

AF:

0.784

Gnomad4 NFE exome

AF:

0.790

Gnomad4 OTH exome

AF:

0.777

GnomAD4 genome

AF:

0.808

AC:

122884

AN:

152168

Hom.:

50200

Cov.:

AF XY:

0.802

AC XY:

59625

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.933

Gnomad4 AMR

AF:

0.693

Gnomad4 ASJ

AF:

0.710

Gnomad4 EAS

AF:

0.633

Gnomad4 SAS

AF:

0.780

Gnomad4 FIN

AF:

0.783

Gnomad4 NFE

AF:

0.784

Gnomad4 OTH

AF:

0.764

Alfa

AF:

0.778

Hom.:

92529

Bravo

AF:

0.801

Asia WGS

AF:

0.751

AC:

2611

AN:

3478

EpiCase

AF:

0.763

EpiControl

AF:

0.762

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Lymphedema-posterior choanal atresia syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.2

DANN

Benign

0.43

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over