Variant chr6-43076502-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002821.5(PTK7):c.14G>T(p.Arg5Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PTK7
NM_002821.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0900

Variant links:

Genes affected

PTK7 (HGNC:9618): (protein tyrosine kinase 7 (inactive)) This gene encodes a member of the receptor protein tyrosine kinase family of proteins that transduce extracellular signals across the cell membrane. The encoded protein lacks detectable catalytic tyrosine kinase activity, is involved in the Wnt signaling pathway and plays a role in multiple cellular processes including polarity and adhesion. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

PTK7 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1509436).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTK7	NM_002821.5 linkuse as main transcript	c.14G>T	p.Arg5Leu	missense_variant	1/20	ENST00000230419.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTK7	ENST00000230419.9 linkuse as main transcript	c.14G>T	p.Arg5Leu	missense_variant	1/20	1	NM_002821.5	P1	Q13308-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1418082

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

705240

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 22, 2023

The c.14G>T (p.R5L) alteration is located in exon 1 (coding exon 1) of the PTK7 gene. This alteration results from a G to T substitution at nucleotide position 14, causing the arginine (R) at amino acid position 5 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.083

T;T;.;.;.;.

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.84

T;T;T;T;T;T

M_CAP

Pathogenic

0.35

MetaRNN

Benign

0.15

T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

N;.;.;N;N;N

MutationTaster

Benign

1.0

N;N;N;N;N;N

PROVEAN

Benign

-0.75

N;N;N;N;N;N

REVEL

Benign

0.060

Sift

Uncertain

0.029

D;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D

Polyphen

0.13

B;.;B;B;B;B

Vest4

0.20

MutPred

0.33

Loss of MoRF binding (P = 9e-04);Loss of MoRF binding (P = 9e-04);Loss of MoRF binding (P = 9e-04);Loss of MoRF binding (P = 9e-04);Loss of MoRF binding (P = 9e-04);Loss of MoRF binding (P = 9e-04);

MVP

0.44

ClinPred

0.099

GERP RS

0.19

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.064

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over