6-43121691-C-T

Variant names:

• chr6-43121691-C-T
• rs3805931
• NM_002821.5:c.80-7286C>T

Variant summary

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

The NM_002821.5(PTK7):​c.80-7286C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 152,086 control chromosomes in the GnomAD database, including 7,877 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 0.32 (7877 hom., cov: 32)
• Consequence: PTK7 NM_002821.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.347 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.80-7286C>T		intron	N/A	NP_002812.2
	PTK7	NM_001270398.2		c.104-7286C>T		intron	N/A	NP_001257327.1	Q13308-6
	PTK7	NM_152880.4		c.80-7286C>T		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.80-7286C>T		intron	N/A	ENSP00000230419.4	Q13308-1
	PTK7	ENST00000345201.6	TSL:1	c.80-7286C>T		intron	N/A	ENSP00000325992.4	Q13308-2
	PTK7	ENST00000352931.6	TSL:1	c.80-7286C>T		intron	N/A	ENSP00000326029.3	Q13308-4

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48151 AN: 151966 Hom.: 7876 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.0633

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.317 AC: 48176 AN: 152086 Hom.: 7877 Cov.: 32 AF XY: 0.307 AC XY: 22858 AN XY: 74356

African (AFR) AF: 0.352 AC: 14587 AN: 41454

American (AMR) AF: 0.260 AC: 3968 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1534 AN: 3472

East Asian (EAS) AF: 0.0639 AC: 331 AN: 5182

South Asian (SAS) AF: 0.264 AC: 1273 AN: 4820

European-Finnish (FIN) AF: 0.253 AC: 2680 AN: 10594

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22716 AN: 67978

Other (OTH) AF: 0.318 AC: 669 AN: 2106

Alfa AF: 0.326 Hom.: 24791

Bravo AF: 0.315

Asia WGS AF: 0.176 AC: 614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.5
DANN	Benign	0.57
PhyloP100		0.13
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: rs3805931; hg19: chr6-43089429;