chr1-214369548-G-A

Position:

• chr1-214369548-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_005401.5(PTPN14):​c.3180C>T​(p.His1060=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,614,084 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (10 hom., cov: 32)
  • Exomes 𝑓: 0.010 (76 hom.)
• Consequence: PTPN14 NM_005401.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.99

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 1-214369548-G-A is Benign according to our data. Variant chr1-214369548-G-A is described in ClinVar as [Benign]. Clinvar id is 775166.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-214369548-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=2.99 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN14	NM_005401.5	c.3180C>T	p.His1060=	synonymous_variant	17/19	ENST00000366956.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN14	ENST00000366956.10	c.3180C>T	p.His1060=	synonymous_variant	17/19	1	NM_005401.5	P1
PTPN14	ENST00000543945.5	c.*2456C>T		3_prime_UTR_variant	16/18	5

Frequencies

GnomAD3 genomes AF: 0.0112 AC: 1698 AN: 152098 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00989

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00415

Gnomad FIN AF: 0.000848

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0114

Gnomad OTH AF: 0.0143

GnomAD3 exomes AF: 0.00954 AC: 2400 AN: 251474 Hom.: 16 AF XY: 0.00963 AC XY: 1309 AN XY: 135912

Gnomad AFR exome AF: 0.0157

Gnomad AMR exome AF: 0.00905

Gnomad ASJ exome AF: 0.0129

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00692

Gnomad FIN exome AF: 0.00143

Gnomad NFE exome AF: 0.0123

Gnomad OTH exome AF: 0.00993

GnomAD4 exome AF: 0.0101 AC: 14720 AN: 1461868 Hom.: 76 Cov.: 37 AF XY: 0.0102 AC XY: 7408 AN XY: 727234

Gnomad4 AFR exome AF: 0.0157

Gnomad4 AMR exome AF: 0.00939

Gnomad4 ASJ exome AF: 0.0132

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00759

Gnomad4 FIN exome AF: 0.00154

Gnomad4 NFE exome AF: 0.0108

Gnomad4 OTH exome AF: 0.0101

GnomAD4 genome AF: 0.0112 AC: 1701 AN: 152216 Hom.: 10 Cov.: 32 AF XY: 0.0102 AC XY: 760 AN XY: 74412

Gnomad4 AFR AF: 0.0158

Gnomad4 AMR AF: 0.00988

Gnomad4 ASJ AF: 0.0144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00415

Gnomad4 FIN AF: 0.000848

Gnomad4 NFE AF: 0.0114

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.0120 Hom.: 7

Bravo AF: 0.0120

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.0134

EpiControl AF: 0.0145

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	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	6.2
DANN	Benign	0.56

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: rs61749332; hg19: chr1-214542891;