rs310644

Positions:

• chr20-63528151-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PTK6	NM_005975.4	c.*1385A>G		3_prime_UTR_variant	8/8	ENST00000542869.3	NP_005966.1
PTK6	NM_001256358.2	c.*2214A>G		3_prime_UTR_variant	7/7		NP_001243287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTK6	ENST00000542869	c.*1385A>G		3_prime_UTR_variant	8/8	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

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

Gnomad4 AFR AF: 0.784

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.0933

Gnomad4 EAS AF: 0.0401

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.0287

Gnomad4 NFE AF: 0.0589

Gnomad4 OTH AF: 0.231

Alfa AF: 0.0945 Hom.: 2832

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

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

LitVar

Other links and lift over

dbSNP: rs310644; hg19: chr20-62159504;