rs1537638

Variant names:

• chr6-43128461-T-C
• rs1537638
• NM_002821.5:c.80-516T>C

Variant summary

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

The NM_002821.5(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 NM_002821.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002821.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTK7	NM_002821.5	MANE Select	c.80-516T>C		intron	N/A	NP_002812.2
	PTK7	NM_001270398.2		c.104-516T>C		intron	N/A	NP_001257327.1	Q13308-6
	PTK7	NM_152880.4		c.80-516T>C		intron	N/A	NP_690619.1	Q13308-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTK7	ENST00000230419.9	TSL:1 MANE Select	c.80-516T>C		intron	N/A	ENSP00000230419.4	Q13308-1
	PTK7	ENST00000345201.6	TSL:1	c.80-516T>C		intron	N/A	ENSP00000325992.4	Q13308-2
	PTK7	ENST00000352931.6	TSL:1	c.80-516T>C		intron	N/A	ENSP00000326029.3	Q13308-4

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

African (AFR) AF: 0.494 AC: 20474 AN: 41476

American (AMR) AF: 0.313 AC: 4777 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1600 AN: 3466

East Asian (EAS) AF: 0.0544 AC: 282 AN: 5188

South Asian (SAS) AF: 0.304 AC: 1470 AN: 4830

European-Finnish (FIN) AF: 0.294 AC: 3121 AN: 10598

Middle Eastern (MID) AF: 0.432 AC: 126 AN: 292

European-Non Finnish (NFE) AF: 0.396 AC: 26904 AN: 67978

Other (OTH) AF: 0.374 AC: 788 AN: 2106

Alfa AF: 0.391 Hom.: 22582

Bravo AF: 0.396

Asia WGS AF: 0.204 AC: 709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	7.7
DANN	Benign	0.89
PhyloP100		0.039
Mutation Taster		=100/0	polymorphism (auto)

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: rs1537638; hg19: chr6-43096199;