1-214364635-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_005401.5(PTPN14):c.3312C>T(p.Asn1104=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000994 in 1,614,104 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0051 (11 hom., cov: 32)
  • Exomes 𝑓: 0.00057 (9 hom.)
• Consequence: PTPN14 NM_005401.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.83

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 1-214364635-G-A is Benign according to our data. Variant chr1-214364635-G-A is described in ClinVar as [Benign]. Clinvar id is 791232.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-214364635-G-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00507 (772/152226) while in subpopulation AFR AF= 0.0173 (719/41546). AF 95% confidence interval is 0.0163. There are 11 homozygotes in gnomad4. There are 367 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN14	NM_005401.5	c.3312C>T	p.Asn1104=	synonymous_variant	18/19	ENST00000366956.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN14	ENST00000366956.10	c.3312C>T	p.Asn1104=	synonymous_variant	18/19	1	NM_005401.5	P1
PTPN14	ENST00000543945.5	c.*2588C>T		3_prime_UTR_variant	17/18	5

Frequencies

GnomAD3 genomes AF: 0.00510 AC: 776 AN: 152108 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.0175

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00149 AC: 374 AN: 251140 Hom.: 3 AF XY: 0.00105 AC XY: 142 AN XY: 135744

Gnomad AFR exome AF: 0.0188

Gnomad AMR exome AF: 0.00145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000881

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.000570 AC: 833 AN: 1461878 Hom.: 9 Cov.: 31 AF XY: 0.000477 AC XY: 347 AN XY: 727244

Gnomad4 AFR exome AF: 0.0191

Gnomad4 AMR exome AF: 0.00132

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000522

Gnomad4 OTH exome AF: 0.00121

GnomAD4 genome AF: 0.00507 AC: 772 AN: 152226 Hom.: 11 Cov.: 32 AF XY: 0.00493 AC XY: 367 AN XY: 74406

Gnomad4 AFR AF: 0.0173

Gnomad4 AMR AF: 0.00235

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00355 Hom.: 2

Bravo AF: 0.00584

Asia WGS AF: 0.00115 AC: 5 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
Cadd	Benign	12
Dann	Benign	0.92

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: rs73074015; hg19: chr1-214537978;