1-214357896-C-T

Variant names:

• chr1-214357896-C-T
• rs2291831
• NM_005401.5:c.*26G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005401.5(PTPN14):​c.*26G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,605,466 control chromosomes in the GnomAD database, including 17,131 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (1937 hom., cov: 32)
  • Exomes 𝑓: 0.14 (15194 hom.)
• Consequence: PTPN14 NM_005401.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.522
• Publications: 10 publications found

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]

PTPN14 Gene-Disease associations (from GenCC):

• lymphedema-posterior choanal atresia syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 1-214357896-C-T is Benign according to our data. Variant chr1-214357896-C-T is described in ClinVar as Benign. ClinVar VariationId is 1180900.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005401.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN14	NM_005401.5	MANE Select	c.*26G>A		3_prime_UTR	Exon 19 of 19	NP_005392.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN14	ENST00000366956.10	TSL:1 MANE Select	c.*26G>A		3_prime_UTR	Exon 19 of 19	ENSP00000355923.4	Q15678
	PTPN14	ENST00000543945.5	TSL:5	c.*2866G>A		3_prime_UTR	Exon 18 of 18	ENSP00000443330.1	E2J9M0

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23714 AN: 152046 Hom.: 1934 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.0905

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.180

GnomAD2 exomes AF: 0.140 AC: 35024 AN: 249788 AF XY: 0.142

Gnomad AFR exome AF: 0.196

Gnomad AMR exome AF: 0.103

Gnomad ASJ exome AF: 0.190

Gnomad EAS exome AF: 0.172

Gnomad FIN exome AF: 0.0978

Gnomad NFE exome AF: 0.141

Gnomad OTH exome AF: 0.166

GnomAD4 exome AF: 0.141 AC: 204254 AN: 1453302 Hom.: 15194 Cov.: 30 AF XY: 0.142 AC XY: 102608 AN XY: 723446

African (AFR) AF: 0.202 AC: 6718 AN: 33262

American (AMR) AF: 0.107 AC: 4774 AN: 44642

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 4974 AN: 26048

East Asian (EAS) AF: 0.167 AC: 6616 AN: 39620

South Asian (SAS) AF: 0.140 AC: 12017 AN: 85814

European-Finnish (FIN) AF: 0.0959 AC: 5114 AN: 53350

Middle Eastern (MID) AF: 0.216 AC: 1015 AN: 4692

European-Non Finnish (NFE) AF: 0.139 AC: 153719 AN: 1105856

Other (OTH) AF: 0.155 AC: 9307 AN: 60018

GnomAD4 genome AF: 0.156 AC: 23740 AN: 152164 Hom.: 1937 Cov.: 32 AF XY: 0.154 AC XY: 11444 AN XY: 74404

African (AFR) AF: 0.199 AC: 8247 AN: 41492

American (AMR) AF: 0.144 AC: 2198 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 670 AN: 3470

East Asian (EAS) AF: 0.171 AC: 884 AN: 5166

South Asian (SAS) AF: 0.130 AC: 626 AN: 4828

European-Finnish (FIN) AF: 0.0905 AC: 960 AN: 10602

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9543 AN: 67986

Other (OTH) AF: 0.177 AC: 374 AN: 2114

Alfa AF: 0.152 Hom.: 3256

Bravo AF: 0.163

Asia WGS AF: 0.122 AC: 425 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Lymphedema-posterior choanal atresia syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	5.9
DANN	Benign	0.80
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2291831; hg19: chr1-214531239; COSMIC: COSV65282346; COSMIC: COSV65282346;