rs139636574

Variant names:

• chr6-43076902-G-A
• rs139636574
• NM_002821.5:c.79+335G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-43076902-G-A
• chr6-43076902-G-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001270398.2(PTK7):​c.19G>A​(p.Gly7Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.01 in 1,511,964 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0090 (11 hom., cov: 32)
  • Exomes 𝑓: 0.010 (78 hom.)
• Consequence: PTK7 NM_001270398.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.879
• Publications: 4 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]

KLC4-AS1 (HGNC:55228): (KLC4 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003965497).
• BP6: Variant 6-43076902-G-A is Benign according to our data. Variant chr6-43076902-G-A is described in ClinVar as Benign. ClinVar VariationId is 2656576.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 1364 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270398.2. 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.79+335G>A		intron	N/A	NP_002812.2
	PTK7	NM_001270398.2		c.19G>A	p.Gly7Arg	missense	Exon 1 of 20	NP_001257327.1	Q13308-6
	PTK7	NM_152880.4		c.79+335G>A		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.79+335G>A		intron	N/A	ENSP00000230419.4	Q13308-1
	PTK7	ENST00000345201.6	TSL:1	c.79+335G>A		intron	N/A	ENSP00000325992.4	Q13308-2
	PTK7	ENST00000352931.6	TSL:1	c.79+335G>A		intron	N/A	ENSP00000326029.3	Q13308-4

Frequencies

GnomAD3 genomes AF: 0.00895 AC: 1363 AN: 152208 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.00212

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0132

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0145

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0127

Gnomad OTH AF: 0.0138

GnomAD2 exomes AF: 0.00645 AC: 812 AN: 125938 AF XY: 0.00609

Gnomad AFR exome AF: 0.00114

Gnomad AMR exome AF: 0.00610

Gnomad ASJ exome AF: 0.00425

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0149

Gnomad NFE exome AF: 0.0102

Gnomad OTH exome AF: 0.0106

GnomAD4 exome AF: 0.0102 AC: 13830 AN: 1359638 Hom.: 78 Cov.: 31 AF XY: 0.0100 AC XY: 6679 AN XY: 667530

African (AFR) AF: 0.00143 AC: 44 AN: 30858

American (AMR) AF: 0.00753 AC: 252 AN: 33464

Ashkenazi Jewish (ASJ) AF: 0.00485 AC: 120 AN: 24754

East Asian (EAS) AF: 0.00 AC: 0 AN: 34674

South Asian (SAS) AF: 0.000617 AC: 48 AN: 77738

European-Finnish (FIN) AF: 0.0178 AC: 596 AN: 33568

Middle Eastern (MID) AF: 0.00302 AC: 17 AN: 5632

European-Non Finnish (NFE) AF: 0.0115 AC: 12191 AN: 1062316

Other (OTH) AF: 0.00992 AC: 562 AN: 56634

GnomAD4 genome AF: 0.00895 AC: 1364 AN: 152326 Hom.: 11 Cov.: 32 AF XY: 0.00913 AC XY: 680 AN XY: 74480

African (AFR) AF: 0.00214 AC: 89 AN: 41578

American (AMR) AF: 0.0132 AC: 202 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.0145 AC: 154 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0127 AC: 864 AN: 68020

Other (OTH) AF: 0.0142 AC: 30 AN: 2116

Alfa AF: 0.00864 Hom.: 1

Bravo AF: 0.00860

TwinsUK AF: 0.0105 AC: 39

ALSPAC AF: 0.00649 AC: 25

ExAC AF: 0.00256 AC: 40

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	PTK7-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	9.4
DANN	Benign	0.93
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.43	T
MetaRNN	Benign	0.0040	T
MetaSVM	Benign	-0.95	T
PhyloP100		0.88
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0050	D
Vest4		0.13
MutPred		0.30		Gain of MoRF binding (P = 0.0019)
MVP		0.068
MPC		0.42
ClinPred		0.072	T
GERP RS		2.4
PromoterAI		-0.077	Neutral
gMVP		0.17
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs139636574; hg19: chr6-43044640;