chr1-214369548-G-A

Variant names:

• chr1-214369548-G-A
• rs61749332
• NM_005401.5:c.3180C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_005401.5(PTPN14):​c.3180C>T​(p.His1060His) 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
• Publications: 2 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 -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 VariationId is 775166.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.99 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

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.3180C>T	p.His1060His	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.3180C>T	p.His1060His	synonymous	Exon 17 of 19	ENSP00000355923.4	Q15678
	PTPN14	ENST00000543945.5	TSL:5	c.*2456C>T		3_prime_UTR	Exon 16 of 18	ENSP00000443330.1	E2J9M0

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

GnomAD2 exomes AF: 0.00954 AC: 2400 AN: 251474 AF XY: 0.00963

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 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

African (AFR) AF: 0.0157 AC: 526 AN: 33480

American (AMR) AF: 0.00939 AC: 420 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0132 AC: 345 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00759 AC: 655 AN: 86258

European-Finnish (FIN) AF: 0.00154 AC: 82 AN: 53420

Middle Eastern (MID) AF: 0.0135 AC: 78 AN: 5768

European-Non Finnish (NFE) AF: 0.0108 AC: 12006 AN: 1111986

Other (OTH) AF: 0.0101 AC: 607 AN: 60396

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

African (AFR) AF: 0.0158 AC: 656 AN: 41544

American (AMR) AF: 0.00988 AC: 151 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0144 AC: 50 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00415 AC: 20 AN: 4818

European-Finnish (FIN) AF: 0.000848 AC: 9 AN: 10612

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0114 AC: 776 AN: 68014

Other (OTH) AF: 0.0142 AC: 30 AN: 2116

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	6.2
DANN	Benign	0.56
PhyloP100		3.0
Mutation Taster		=99/1	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

Other links and lift over

dbSNP: rs61749332; hg19: chr1-214542891;