20-63530141-C-T
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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):c.1105G>A(p.Asp369Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,614,070 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 (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
PTK6
NM_005975.4 missense
NM_005975.4 missense
Scores
10
4
3
Clinical Significance
Conservation
PhyloP100: 7.43
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, 0.99
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTK6 | NM_005975.4 | c.1105G>A | p.Asp369Asn | missense_variant | 7/8 | ENST00000542869.3 | |
PTK6 | NM_001256358.2 | c.*578G>A | 3_prime_UTR_variant | 6/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTK6 | ENST00000542869.3 | c.1105G>A | p.Asp369Asn | missense_variant | 7/8 | 1 | NM_005975.4 | P1 | |
PTK6 | ENST00000217185.3 | c.*578G>A | 3_prime_UTR_variant | 6/7 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152188Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000120 AC: 3AN: 251010Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135872
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GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461764Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727182
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GnomAD4 genome AF: 0.0000328 AC: 5AN: 152306Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74480
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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 | May 09, 2023 | The c.1105G>A (p.D369N) alteration is located in exon 7 (coding exon 7) of the PTK6 gene. This alteration results from a G to A substitution at nucleotide position 1105, causing the aspartic acid (D) at amino acid position 369 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Pathogenic
D
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
REVEL
Pathogenic
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MVP
ClinPred
D
GERP RS
Varity_R
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