20-63530147-T-C
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_005975.4(PTK6):āc.1099A>Gā(p.Lys367Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000186 in 1,614,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.000020 ( 0 hom. )
Consequence
PTK6
NM_005975.4 missense
NM_005975.4 missense
Scores
3
9
5
Clinical Significance
Conservation
PhyloP100: 5.82
Genes affected
PTK6 (HGNC:9617): (protein tyrosine kinase 6) The protein encoded by this gene is a cytoplasmic nonreceptor protein kinase which may function as an intracellular signal transducer in epithelial tissues. Overexpression of this gene in mammary epithelial cells leads to sensitization of the cells to epidermal growth factor and results in a partially transformed phenotype. Expression of this gene has been detected at low levels in some breast tumors but not in normal breast tissue. The encoded protein has been shown to undergo autophosphorylation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2012]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.983
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTK6 | NM_005975.4 | c.1099A>G | p.Lys367Glu | missense_variant | 7/8 | ENST00000542869.3 | |
PTK6 | NM_001256358.2 | c.*572A>G | 3_prime_UTR_variant | 6/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTK6 | ENST00000542869.3 | c.1099A>G | p.Lys367Glu | missense_variant | 7/8 | 1 | NM_005975.4 | P1 | |
PTK6 | ENST00000217185.3 | c.*572A>G | 3_prime_UTR_variant | 6/7 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152230Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.0000198 AC: 29AN: 1461774Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9AN XY: 727186
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152230Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74384
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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 | Apr 08, 2022 | The c.1099A>G (p.K367E) alteration is located in exon 7 (coding exon 7) of the PTK6 gene. This alteration results from a A to G substitution at nucleotide position 1099, causing the lysine (K) at amino acid position 367 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Pathogenic
D
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Benign
M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
REVEL
Uncertain
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Loss of ubiquitination at K367 (P = 0.0183);
MVP
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at