4-3493307-G-C
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4
The NM_173660.5(DOK7):c.1321G>C(p.Gly441Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000374 in 1,605,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G441E) has been classified as Uncertain significance.
Frequency
Consequence
NM_173660.5 missense
Scores
Clinical Significance
Conservation
Publications
- congenital myasthenic syndrome 10Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia
- fetal akinesia deformation sequence 3Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
- fetal akinesia deformation sequence 1Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- postsynaptic congenital myasthenic syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Uncertain_significance. The variant received 1 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DOK7 | ENST00000340083.6 | c.1321G>C | p.Gly441Arg | missense_variant | Exon 7 of 7 | 1 | NM_173660.5 | ENSP00000344432.5 | ||
DOK7 | ENST00000643608.1 | c.889G>C | p.Gly297Arg | missense_variant | Exon 5 of 8 | ENSP00000495701.1 | ||||
DOK7 | ENST00000515886.5 | c.391G>C | p.Gly131Arg | missense_variant | Exon 4 of 4 | 2 | ENSP00000492194.1 | |||
DOK7 | ENST00000507039.5 | c.*542G>C | 3_prime_UTR_variant | Exon 7 of 7 | 2 | ENSP00000423614.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152222Hom.: 0 Cov.: 34 show subpopulations
GnomAD2 exomes AF: 0.0000135 AC: 3AN: 221834 AF XY: 0.0000163 show subpopulations
GnomAD4 exome AF: 0.00000344 AC: 5AN: 1453620Hom.: 0 Cov.: 95 AF XY: 0.00000554 AC XY: 4AN XY: 722390 show subpopulations
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152222Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74366 show subpopulations
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.1321G>C (p.G441R) alteration is located in exon 7 (coding exon 7) of the DOK7 gene. This alteration results from a G to C substitution at nucleotide position 1321, causing the glycine (G) at amino acid position 441 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at