1-214369755-A-G

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.3037-64T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,416,236 control chromosomes in the GnomAD database, including 27,594 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2353 hom., cov: 32)
  • Exomes 𝑓: 0.19 (25241 hom.)
• Consequence: PTPN14 NM_005401.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0160

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=-0.83).
• BP6: Variant 1-214369755-A-G is Benign according to our data. Variant chr1-214369755-A-G is described in ClinVar as [Benign]. Clinvar id is 1224243.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN14	NM_005401.5	c.3037-64T>C		intron_variant		ENST00000366956.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN14	ENST00000366956.10	c.3037-64T>C		intron_variant		1	NM_005401.5	P1
PTPN14	ENST00000543945.5	c.*2313-64T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25232 AN: 152072 Hom.: 2355 Cov.: 32

Gnomad AFR AF: 0.0886

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.165

GnomAD4 exome AF: 0.194 AC: 245760 AN: 1264046 Hom.: 25241 AF XY: 0.190 AC XY: 121212 AN XY: 637368

Gnomad4 AFR exome AF: 0.0893

Gnomad4 AMR exome AF: 0.219

Gnomad4 ASJ exome AF: 0.142

Gnomad4 EAS exome AF: 0.271

Gnomad4 SAS exome AF: 0.0945

Gnomad4 FIN exome AF: 0.232

Gnomad4 NFE exome AF: 0.203

Gnomad4 OTH exome AF: 0.185

GnomAD4 genome AF: 0.166 AC: 25232 AN: 152190 Hom.: 2353 Cov.: 32 AF XY: 0.166 AC XY: 12312 AN XY: 74390

Gnomad4 AFR AF: 0.0884

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.255

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.164

Alfa AF: 0.189 Hom.: 4773

Bravo AF: 0.159

Asia WGS AF: 0.192 AC: 667 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	5.3
Dann	Benign	0.65

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: rs3738425; hg19: chr1-214543098; COSMIC: COSV65282320; COSMIC: COSV65282320;