1-214364206-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005401.5(PTPN14):c.3435+306G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,120 control chromosomes in the GnomAD database, including 2,067 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (2067 hom., cov: 32)
• Consequence: PTPN14 NM_005401.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.241

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-214364206-C-T is Benign according to our data. Variant chr1-214364206-C-T is described in ClinVar as [Benign]. Clinvar id is 1231393.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN14	NM_005401.5	c.3435+306G>A		intron_variant		ENST00000366956.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN14	ENST00000366956.10	c.3435+306G>A		intron_variant		1	NM_005401.5	P1
PTPN14	ENST00000543945.5	c.*2711+306G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22090 AN: 152002 Hom.: 2070 Cov.: 32

Gnomad AFR AF: 0.0340

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.145 AC: 22086 AN: 152120 Hom.: 2067 Cov.: 32 AF XY: 0.145 AC XY: 10797 AN XY: 74338

Gnomad4 AFR AF: 0.0339

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.151

Alfa AF: 0.176 Hom.: 454

Bravo AF: 0.138

Asia WGS AF: 0.176 AC: 614 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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	-0.90
Cadd	Benign	3.3
Dann	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs11120303; hg19: chr1-214537549; COSMIC: COSV65288201;