20-63528151-T-C

Variant names:

• chr20-63528151-T-C
• rs310644
• NM_005975.4:c.*1385A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005975.4(PTK6):​c.*1385A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,182 control chromosomes in the GnomAD database, including 13,578 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.27 (13578 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: PTK6 NM_005975.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137
• Publications: 21 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTK6	NM_005975.4	c.*1385A>G		3_prime_UTR_variant	Exon 8 of 8	ENST00000542869.3	NP_005966.1
PTK6	NM_001256358.2	c.*2214A>G		3_prime_UTR_variant	Exon 7 of 7		NP_001243287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTK6	ENST00000542869.3	c.*1385A>G		3_prime_UTR_variant	Exon 8 of 8	1	NM_005975.4	ENSP00000442460.2

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41374 AN: 152064 Hom.: 13507 Cov.: 33

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.0933

Gnomad EAS AF: 0.0402

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.0287

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0590

Gnomad OTH AF: 0.222

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.273 AC: 41509 AN: 152182 Hom.: 13578 Cov.: 33 AF XY: 0.266 AC XY: 19794 AN XY: 74410

African (AFR) AF: 0.784 AC: 32542 AN: 41494

American (AMR) AF: 0.131 AC: 2001 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0933 AC: 324 AN: 3472

East Asian (EAS) AF: 0.0401 AC: 208 AN: 5192

South Asian (SAS) AF: 0.326 AC: 1567 AN: 4814

European-Finnish (FIN) AF: 0.0287 AC: 305 AN: 10610

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0589 AC: 4008 AN: 68006

Other (OTH) AF: 0.231 AC: 486 AN: 2108

Alfa AF: 0.134 Hom.: 13791

Bravo AF: 0.299

Asia WGS AF: 0.328 AC: 1140 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.6
DANN	Benign	0.56
PhyloP100		0.14

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

Other links and lift over

dbSNP: rs310644; hg19: chr20-62159504;