rs1460965413

Variant names:

• chr6-43129244-A-C
• rs1460965413
• NM_002821.5:c.347A>C

Your query was ambiguous. Multiple possible variants found:

• chr6-43129244-A-C
• chr6-43129244-A-G
• chr6-43129244-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002821.5(PTK7):​c.347A>C​(p.Asn116Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N116I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PTK7 NM_002821.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.71
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23857039).

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.347A>C	p.Asn116Thr	missense	Exon 2 of 20	NP_002812.2
	PTK7	NM_001270398.2		c.371A>C	p.Asn124Thr	missense	Exon 2 of 20	NP_001257327.1	Q13308-6
	PTK7	NM_152880.4		c.347A>C	p.Asn116Thr	missense	Exon 2 of 19	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.347A>C	p.Asn116Thr	missense	Exon 2 of 20	ENSP00000230419.4	Q13308-1
	PTK7	ENST00000345201.6	TSL:1	c.347A>C	p.Asn116Thr	missense	Exon 2 of 19	ENSP00000325992.4	Q13308-2
	PTK7	ENST00000352931.6	TSL:1	c.347A>C	p.Asn116Thr	missense	Exon 2 of 19	ENSP00000326029.3	Q13308-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461810 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727208

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53340

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.4	L
PhyloP100		5.7
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.19
Sift	Benign	0.26	T
Sift4G	Benign	0.082	T
Polyphen		0.97	D
Vest4		0.42
MutPred		0.36		Gain of sheet (P = 0.0827)
MVP		0.45
MPC		0.37
ClinPred		0.83	D
GERP RS		5.0
Varity_R		0.078
gMVP		0.44
Mutation Taster		=50/50

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: rs1460965413; hg19: chr6-43096982;