rs759054772

Variant names:

• chr4-3463420-C-A
• rs759054772
• NM_173660.5:c.45C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-3463420-C-A
• chr4-3463420-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_173660.5(DOK7):​c.45C>A​(p.Asp15Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. D15N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DOK7 NM_173660.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.521

Genes affected

DOK7 (HGNC:26594): (docking protein 7) The protein encoded by this gene is essential for neuromuscular synaptogenesis. The protein functions in aneural activation of muscle-specific receptor kinase, which is required for postsynaptic differentiation, and in the subsequent clustering of the acetylcholine receptor in myotubes. This protein can also induce autophosphorylation of muscle-specific receptor kinase. Mutations in this gene are a cause of familial limb-girdle myasthenia autosomal recessive, which is also known as congenital myasthenic syndrome type 1B. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOK7	NM_173660.5	c.45C>A	p.Asp15Glu	missense_variant	Exon 1 of 7	ENST00000340083.6	NP_775931.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOK7	ENST00000340083.6	c.45C>A	p.Asp15Glu	missense_variant	Exon 1 of 7	1	NM_173660.5	ENSP00000344432.5

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1228388 Hom.: 0 Cov.: 48 AF XY: 0.00 AC XY: 0 AN XY: 605642

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.088	.;T;.
Eigen	Benign	-0.070
Eigen_PC	Benign	-0.077
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.80	T;T;T
M_CAP	Pathogenic	0.71	D
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.7	L;L;.
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-2.1	N;N;.
REVEL	Benign	0.18
Sift	Benign	0.23	T;T;.
Sift4G	Benign	0.21	T;T;.
Polyphen		0.94	.;P;.
Vest4		0.33
MutPred		0.28		Gain of methylation at K18 (P = 0.0739);Gain of methylation at K18 (P = 0.0739);Gain of methylation at K18 (P = 0.0739);
MVP		0.80
MPC		0.0047
ClinPred		0.60	D
GERP RS		1.4
Varity_R		0.12
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.30		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.30		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs759054772; hg19: chr4-3465147;