1-214372417-T-G

Position:

• chr1-214372417-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005401.5(PTPN14):​c.3036+294A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 337,504 control chromosomes in the GnomAD database, including 9,219 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3741 hom., cov: 32)
  • Exomes 𝑓: 0.23 (5478 hom.)
• Consequence: PTPN14 NM_005401.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.265

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-214372417-T-G is Benign according to our data. Variant chr1-214372417-T-G is described in ClinVar as [Benign]. Clinvar id is 1272798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN14	NM_005401.5	c.3036+294A>C		intron_variant		ENST00000366956.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN14	ENST00000366956.10	c.3036+294A>C		intron_variant		1	NM_005401.5	P1
PTPN14	ENST00000543945.5	c.*2312+294A>C		intron_variant		5
PTPN14	ENST00000473261.1	n.318-47A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30841 AN: 152016 Hom.: 3740 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.170

GnomAD4 exome AF: 0.228 AC: 42238 AN: 185370 Hom.: 5478 Cov.: 3 AF XY: 0.216 AC XY: 21686 AN XY: 100244

Gnomad4 AFR exome AF: 0.0954

Gnomad4 AMR exome AF: 0.194

Gnomad4 ASJ exome AF: 0.162

Gnomad4 EAS exome AF: 0.00212

Gnomad4 SAS exome AF: 0.148

Gnomad4 FIN exome AF: 0.286

Gnomad4 NFE exome AF: 0.271

Gnomad4 OTH exome AF: 0.230

GnomAD4 genome AF: 0.203 AC: 30858 AN: 152134 Hom.: 3741 Cov.: 32 AF XY: 0.199 AC XY: 14822 AN XY: 74376

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.170

Alfa AF: 0.153 Hom.: 375

Bravo AF: 0.192

Asia WGS AF: 0.0760 AC: 268 AN: 3478

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	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.0
DANN	Benign	0.74

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: rs72757957; hg19: chr1-214545760;