1-214376158-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.2907+61G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.097 in 1,479,900 control chromosomes in the GnomAD database, including 7,996 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1209 hom., cov: 32)
  • Exomes 𝑓: 0.095 (6787 hom.)
• Consequence: PTPN14 NM_005401.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.54

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 1-214376158-C-T is Benign according to our data. Variant chr1-214376158-C-T is described in ClinVar as [Benign]. Clinvar id is 1243860.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN14	NM_005401.5	c.2907+61G>A		intron_variant		ENST00000366956.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN14	ENST00000366956.10	c.2907+61G>A		intron_variant		1	NM_005401.5	P1
PTPN14	ENST00000543945.5	c.*2183+61G>A		intron_variant		5
PTPN14	ENST00000473261.1	n.188+61G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17659 AN: 151998 Hom.: 1202 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0863

Gnomad ASJ AF: 0.0798

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0835

Gnomad OTH AF: 0.114

GnomAD4 exome AF: 0.0948 AC: 125926 AN: 1327784 Hom.: 6787 AF XY: 0.0971 AC XY: 64348 AN XY: 662434

Gnomad4 AFR exome AF: 0.184

Gnomad4 AMR exome AF: 0.0589

Gnomad4 ASJ exome AF: 0.0846

Gnomad4 EAS exome AF: 0.148

Gnomad4 SAS exome AF: 0.169

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.0848

Gnomad4 OTH exome AF: 0.107

GnomAD4 genome AF: 0.116 AC: 17688 AN: 152116 Hom.: 1209 Cov.: 32 AF XY: 0.118 AC XY: 8810 AN XY: 74362

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.0861

Gnomad4 ASJ AF: 0.0798

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.0835

Gnomad4 OTH AF: 0.118

Alfa AF: 0.0882 Hom.: 712

Bravo AF: 0.115

Asia WGS AF: 0.194 AC: 671 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

Jun 20, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.34
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: rs1125452; hg19: chr1-214549501; COSMIC: COSV65281356;