Genetic Variant PTK7:c.79+402C>A (chr6-43076969-C-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001270398.2(PTK7):c.86C>A(p.Pro29His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00475 in 1,508,026 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0038 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0048 ( 19 hom. )

Consequence

PTK7
NM_001270398.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.206

Publications

5 publications found

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:

KLC4-AS1 (HGNC:55228): (KLC4 antisense RNA 1)

KLC4-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0041211247).

BP6

Variant 6-43076969-C-A is Benign according to our data. Variant chr6-43076969-C-A is described in ClinVar as Benign. ClinVar VariationId is 3050084.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 582 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270398.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTK7	NM_002821.5	MANE Select	c.79+402C>A		intron	N/A	NP_002812.2
PTK7	NM_001270398.2		c.86C>A	p.Pro29His	missense	Exon 1 of 20	NP_001257327.1	Q13308-6
PTK7	NM_152880.4		c.79+402C>A		intron	N/A	NP_690619.1	Q13308-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PTK7	ENST00000230419.9	TSL:1 MANE Select	c.79+402C>A	intron	N/A	ENSP00000230419.4	Q13308-1
PTK7	ENST00000345201.6	TSL:1	c.79+402C>A	intron	N/A	ENSP00000325992.4	Q13308-2
PTK7	ENST00000352931.6	TSL:1	c.79+402C>A	intron	N/A	ENSP00000326029.3	Q13308-4

Frequencies

GnomAD3 genomes

AF:

0.00382

AC:

582

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.000719

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00227

Gnomad FIN

AF:

0.0112

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00570

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00333

AC:

414

AN:

124278

AF XY:

0.00363

show subpopulations

Gnomad AFR exome

AF:

0.000501

Gnomad AMR exome

AF:

0.000866

Gnomad ASJ exome

AF:

0.00114

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0131

Gnomad NFE exome

AF:

0.00563

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00485

AC:

6574

AN:

1355670

Hom.:

Cov.:

AF XY:

0.00472

AC XY:

3138

AN XY:

665256

show subpopulations

African (AFR)

AF:

0.000618

AC:

AN:

30746

American (AMR)

AF:

0.000916

AC:

AN:

33844

Ashkenazi Jewish (ASJ)

AF:

0.000650

AC:

AN:

24616

East Asian (EAS)

AF:

0.00

AC:

AN:

34372

South Asian (SAS)

AF:

0.00142

AC:

109

AN:

76950

European-Finnish (FIN)

AF:

0.0118

AC:

395

AN:

33440

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5610

European-Non Finnish (NFE)

AF:

0.00547

AC:

5799

AN:

1059702

Other (OTH)

AF:

0.00364

AC:

205

AN:

56390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

336

673

1009

1346

1682

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

210

420

630

840

1050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00382

AC:

582

AN:

152356

Hom.:

Cov.:

AF XY:

0.00387

AC XY:

288

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.000745

AC:

AN:

41584

American (AMR)

AF:

0.000718

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00228

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0112

AC:

119

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00570

AC:

388

AN:

68032

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

127

159

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00112

Hom.:

Bravo

AF:

0.00313

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00519

AC:

ExAC

AF:

0.00161

AC:

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

PTK7-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.51

CADD

Benign

2.9

(source)

DANN

Benign

0.95

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.25

MetaRNN

Benign

0.0041

MetaSVM

Benign

-0.99

PhyloP100

-0.21

PrimateAI

Benign

0.32

PROVEAN

Benign

0.13

REVEL

Benign

0.11

Sift

Uncertain

0.029

Sift4G

Benign

0.061

Vest4

0.18

MVP

0.18

MPC

0.41

ClinPred

0.016

GERP RS

1.6

PromoterAI

0.014

Neutral

(source)

gMVP

0.14

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over