1-214369325-T-C

Position:

• chr1-214369325-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005401.5(PTPN14):​c.3271+132A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 766,546 control chromosomes in the GnomAD database, including 234,695 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.81 (50210 hom., cov: 33)
  • Exomes 𝑓: 0.77 (184485 hom.)
• Consequence: PTPN14 NM_005401.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.53

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 1-214369325-T-C is Benign according to our data. Variant chr1-214369325-T-C is described in ClinVar as [Benign]. Clinvar id is 1278557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.3271+132A>G		intron_variant		ENST00000366956.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN14	ENST00000366956.10	c.3271+132A>G		intron_variant		1	NM_005401.5	P1
PTPN14	ENST00000543945.5	c.*2547+132A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.807 AC: 122814 AN: 152110 Hom.: 50157 Cov.: 33

Gnomad AFR AF: 0.933

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.780

Gnomad FIN AF: 0.783

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.762

GnomAD4 exome AF: 0.773 AC: 474828 AN: 614318 Hom.: 184485 AF XY: 0.773 AC XY: 247344 AN XY: 319922

Gnomad4 AFR exome AF: 0.934

Gnomad4 AMR exome AF: 0.677

Gnomad4 ASJ exome AF: 0.712

Gnomad4 EAS exome AF: 0.613

Gnomad4 SAS exome AF: 0.787

Gnomad4 FIN exome AF: 0.785

Gnomad4 NFE exome AF: 0.785

Gnomad4 OTH exome AF: 0.775

GnomAD4 genome AF: 0.807 AC: 122921 AN: 152228 Hom.: 50210 Cov.: 33 AF XY: 0.801 AC XY: 59639 AN XY: 74414

Gnomad4 AFR AF: 0.933

Gnomad4 AMR AF: 0.693

Gnomad4 ASJ AF: 0.711

Gnomad4 EAS AF: 0.632

Gnomad4 SAS AF: 0.780

Gnomad4 FIN AF: 0.783

Gnomad4 NFE AF: 0.784

Gnomad4 OTH AF: 0.764

Alfa AF: 0.812 Hom.: 6247

Bravo AF: 0.801

Asia WGS AF: 0.751 AC: 2610 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0050
DANN	Benign	0.49

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: rs3002311; hg19: chr1-214542668;