rs1537638

Positions:

• chr6-43128461-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000230419.9(PTK7):​c.80-516T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 152,130 control chromosomes in the GnomAD database, including 12,439 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 0.39 (12439 hom., cov: 33)
• Consequence: PTK7 ENST00000230419.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTK7	NM_002821.5	c.80-516T>C		intron_variant		ENST00000230419.9	NP_002812.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTK7	ENST00000230419.9	c.80-516T>C		intron_variant		1	NM_002821.5	ENSP00000230419	P1

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59844 AN: 152010 Hom.: 12432 Cov.: 33

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.0538

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.376

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.394 AC: 59891 AN: 152130 Hom.: 12439 Cov.: 33 AF XY: 0.382 AC XY: 28391 AN XY: 74394

Gnomad4 AFR AF: 0.494

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.462

Gnomad4 EAS AF: 0.0544

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.396

Gnomad4 OTH AF: 0.374

Alfa AF: 0.392 Hom.: 16398

Bravo AF: 0.396

Asia WGS AF: 0.204 AC: 709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	7.7
DANN	Benign	0.89

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: rs1537638; hg19: chr6-43096199;