1-214369476-T-C

Variant names:

• chr1-214369476-T-C
• rs1135352
• NM_005401.5:c.3252A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005401.5(PTPN14):​c.3252A>G​(p.Glu1084Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 1,613,800 control chromosomes in the GnomAD database, including 498,283 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.81 (50200 hom., cov: 32)
  • Exomes 𝑓: 0.78 (448083 hom.)
• Consequence: PTPN14 NM_005401.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0750
• Publications: 24 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-214369476-T-C is Benign according to our data. Variant chr1-214369476-T-C is described in ClinVar as Benign. ClinVar VariationId is 1263765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.075 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.925 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.3252A>G	p.Glu1084Glu	synonymous	Exon 17 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.3252A>G	p.Glu1084Glu	synonymous	Exon 17 of 19	ENSP00000355923.4	Q15678
	PTPN14	ENST00000543945.5	TSL:5	c.*2528A>G		3_prime_UTR	Exon 16 of 18	ENSP00000443330.1	E2J9M0

Frequencies

GnomAD3 genomes AF: 0.807 AC: 122777 AN: 152050 Hom.: 50147 Cov.: 32

Gnomad AFR AF: 0.932

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.781

Gnomad FIN AF: 0.783

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.762

GnomAD2 exomes AF: 0.759 AC: 190876 AN: 251398 AF XY: 0.760

Gnomad AFR exome AF: 0.938

Gnomad AMR exome AF: 0.649

Gnomad ASJ exome AF: 0.708

Gnomad EAS exome AF: 0.621

Gnomad FIN exome AF: 0.786

Gnomad NFE exome AF: 0.784

Gnomad OTH exome AF: 0.747

GnomAD4 exome AF: 0.781 AC: 1142047 AN: 1461632 Hom.: 448083 Cov.: 52 AF XY: 0.780 AC XY: 567475 AN XY: 727118

African (AFR) AF: 0.940 AC: 31455 AN: 33480

American (AMR) AF: 0.652 AC: 29152 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.710 AC: 18553 AN: 26134

East Asian (EAS) AF: 0.610 AC: 24195 AN: 39696

South Asian (SAS) AF: 0.781 AC: 67323 AN: 86252

European-Finnish (FIN) AF: 0.784 AC: 41887 AN: 53420

Middle Eastern (MID) AF: 0.681 AC: 3927 AN: 5766

European-Non Finnish (NFE) AF: 0.790 AC: 878637 AN: 1111780

Other (OTH) AF: 0.777 AC: 46918 AN: 60380

GnomAD4 genome AF: 0.808 AC: 122884 AN: 152168 Hom.: 50200 Cov.: 32 AF XY: 0.802 AC XY: 59625 AN XY: 74390

African (AFR) AF: 0.933 AC: 38741 AN: 41544

American (AMR) AF: 0.693 AC: 10594 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.710 AC: 2464 AN: 3468

East Asian (EAS) AF: 0.633 AC: 3262 AN: 5156

South Asian (SAS) AF: 0.780 AC: 3762 AN: 4820

European-Finnish (FIN) AF: 0.783 AC: 8289 AN: 10582

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.784 AC: 53309 AN: 67996

Other (OTH) AF: 0.764 AC: 1616 AN: 2114

Alfa AF: 0.787 Hom.: 194632

Bravo AF: 0.801

Asia WGS AF: 0.751 AC: 2611 AN: 3478

EpiCase AF: 0.763

EpiControl AF: 0.762

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	-0.80
CADD	Benign	5.2
DANN	Benign	0.43
PhyloP100		0.075
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1135352; hg19: chr1-214542819; COSMIC: COSV65282352; COSMIC: COSV65282352;