1-214369476-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0750

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 -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	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	c.3252A>G	p.Glu1084=	synonymous_variant	17/19	1	NM_005401.5	P1
PTPN14	ENST00000543945.5	c.*2528A>G		3_prime_UTR_variant	16/18	5

Frequencies

GnomAD3 genomes AF: 0.807 AC: 122777 AN: 152050 Hom.: 50147 Cov.: 32

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

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.: 52 AF XY: 0.780 AC XY: 567475 AN XY: 727118

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.: 32 AF XY: 0.802 AC XY: 59625 AN XY: 74390

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Lymphedema-posterior choanal atresia syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

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

Other links and lift over

dbSNP: rs1135352; hg19: chr1-214542819; COSMIC: COSV65282352; COSMIC: COSV65282352;