4-3492905-G-T

Variant names:

• chr4-3492905-G-T
• NM_173660.5:c.919G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173660.5(DOK7):​c.919G>T​(p.Ala307Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,422,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DOK7 NM_173660.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0356566).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOK7	NM_173660.5	c.919G>T	p.Ala307Ser	missense_variant	Exon 7 of 7	ENST00000340083.6	NP_775931.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOK7	ENST00000340083.6	c.919G>T	p.Ala307Ser	missense_variant	Exon 7 of 7	1	NM_173660.5	ENSP00000344432.5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1422318 Hom.: 0 Cov.: 110 AF XY: 0.00000142 AC XY: 1 AN XY: 704686

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: 0.00000183

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	1.7
DANN	Benign	0.71
DEOGEN2	Benign	0.021	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.31	T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.036	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.050	N;.
REVEL	Benign	0.027
Sift	Benign	0.42	T;.
Sift4G	Benign	0.48	T;.
Polyphen		0.0	B;.
Vest4		0.031
MutPred		0.26		Gain of relative solvent accessibility (P = 0.0479);.;
MVP		0.27
MPC		0.0047
ClinPred		0.031	T
GERP RS		2.2
Varity_R		0.033
gMVP		0.072

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-3494632;