1-214364635-G-A

Variant names:

• chr1-214364635-G-A
• rs73074015
• NM_005401.5:c.3312C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_005401.5(PTPN14):​c.3312C>T​(p.Asn1104Asn) 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, multiple submitters, no conflicts B:2
• 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

Our verdict: Benign. The variant received -18 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_multiple_submitters_no_conflicts, 2 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 the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN14	NM_005401.5	c.3312C>T	p.Asn1104Asn	synonymous_variant	Exon 18 of 19	ENST00000366956.10	NP_005392.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN14	ENST00000366956.10	c.3312C>T	p.Asn1104Asn	synonymous_variant	Exon 18 of 19	1	NM_005401.5	ENSP00000355923.4
PTPN14	ENST00000543945	c.*2588C>T		3_prime_UTR_variant	Exon 17 of 18	5		ENSP00000443330.1

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

GnomAD2 exomes AF: 0.00149 AC: 374 AN: 251140 AF XY: 0.00105

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 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 AC: 638 AN: 33480

Gnomad4 AMR exome AF: 0.00132 AC: 59 AN: 44720

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26136

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39700

Gnomad4 SAS exome AF: 0.0000116 AC: 1 AN: 86256

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53418

Gnomad4 NFE exome AF: 0.0000522 AC: 58 AN: 1112008

Gnomad4 Remaining exome AF: 0.00121 AC: 73 AN: 60396

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 AC: 0.0173061 AN: 0.0173061

Gnomad4 AMR AF: 0.00235 AC: 0.00235386 AN: 0.00235386

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.0000882 AC: 0.0000881834 AN: 0.0000881834

Gnomad4 OTH AF: 0.00473 AC: 0.00473485 AN: 0.00473485

Alfa AF: 0.00322 Hom.: 3

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	12
DANN	Benign	0.92
Mutation Taster		=92/8	polymorphism

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;