rs10779614

Variant names:

• chr1-214416571-A-G
• rs10779614
• NM_005401.5:c.345-1845T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-214416571-A-G
• chr1-214416571-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005401.5(PTPN14):​c.345-1845T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 152,024 control chromosomes in the GnomAD database, including 41,731 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.74 (41731 hom., cov: 31)
• Consequence: PTPN14 NM_005401.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.29
• Publications: 3 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.756 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN14	NM_005401.5	MANE Select	c.345-1845T>C		intron	N/A	NP_005392.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN14	ENST00000366956.10	TSL:1 MANE Select	c.345-1845T>C		intron	N/A	ENSP00000355923.4
	PTPN14	ENST00000543945.5	TSL:5	c.345-1845T>C		intron	N/A	ENSP00000443330.1

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112491 AN: 151906 Hom.: 41701 Cov.: 31

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.743

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.761

Gnomad OTH AF: 0.707

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.741 AC: 112574 AN: 152024 Hom.: 41731 Cov.: 31 AF XY: 0.740 AC XY: 54944 AN XY: 74288

African (AFR) AF: 0.732 AC: 30338 AN: 41452

American (AMR) AF: 0.728 AC: 11109 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.670 AC: 2324 AN: 3470

East Asian (EAS) AF: 0.611 AC: 3152 AN: 5162

South Asian (SAS) AF: 0.743 AC: 3577 AN: 4812

European-Finnish (FIN) AF: 0.743 AC: 7839 AN: 10548

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.761 AC: 51746 AN: 67992

Other (OTH) AF: 0.709 AC: 1498 AN: 2114

Alfa AF: 0.749 Hom.: 186836

Bravo AF: 0.739

Asia WGS AF: 0.717 AC: 2494 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.099
DANN	Benign	0.39
PhyloP100		-4.3
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: rs10779614; hg19: chr1-214589914;