chr4-3463346-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_173660.5(DOK7):​c.-30G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,447,188 control chromosomes in the GnomAD database, including 8,816 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.076 ( 678 hom., cov: 32)
Exomes 𝑓: 0.10 ( 8138 hom. )

Consequence

DOK7
NM_173660.5 5_prime_UTR

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.61
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
Variant 4-3463346-G-T is Benign according to our data. Variant chr4-3463346-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 262861.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-3463346-G-T is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DOK7NM_173660.5 linkuse as main transcriptc.-30G>T 5_prime_UTR_variant 1/7 ENST00000340083.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DOK7ENST00000340083.6 linkuse as main transcriptc.-30G>T 5_prime_UTR_variant 1/71 NM_173660.5 P1Q18PE1-1

Frequencies

GnomAD3 genomes
AF:
0.0759
AC:
11521
AN:
151812
Hom.:
677
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0176
Gnomad AMI
AF:
0.0352
Gnomad AMR
AF:
0.0858
Gnomad ASJ
AF:
0.128
Gnomad EAS
AF:
0.0280
Gnomad SAS
AF:
0.228
Gnomad FIN
AF:
0.0810
Gnomad MID
AF:
0.0828
Gnomad NFE
AF:
0.0993
Gnomad OTH
AF:
0.0681
GnomAD3 exomes
AF:
0.113
AC:
9379
AN:
83258
Hom.:
698
AF XY:
0.118
AC XY:
5632
AN XY:
47570
show subpopulations
Gnomad AFR exome
AF:
0.0153
Gnomad AMR exome
AF:
0.116
Gnomad ASJ exome
AF:
0.116
Gnomad EAS exome
AF:
0.0322
Gnomad SAS exome
AF:
0.234
Gnomad FIN exome
AF:
0.0818
Gnomad NFE exome
AF:
0.107
Gnomad OTH exome
AF:
0.101
GnomAD4 exome
AF:
0.105
AC:
135896
AN:
1295270
Hom.:
8138
Cov.:
32
AF XY:
0.108
AC XY:
68873
AN XY:
637794
show subpopulations
Gnomad4 AFR exome
AF:
0.0151
Gnomad4 AMR exome
AF:
0.104
Gnomad4 ASJ exome
AF:
0.114
Gnomad4 EAS exome
AF:
0.0213
Gnomad4 SAS exome
AF:
0.231
Gnomad4 FIN exome
AF:
0.0742
Gnomad4 NFE exome
AF:
0.103
Gnomad4 OTH exome
AF:
0.101
GnomAD4 genome
AF:
0.0759
AC:
11527
AN:
151918
Hom.:
678
Cov.:
32
AF XY:
0.0784
AC XY:
5820
AN XY:
74246
show subpopulations
Gnomad4 AFR
AF:
0.0175
Gnomad4 AMR
AF:
0.0863
Gnomad4 ASJ
AF:
0.128
Gnomad4 EAS
AF:
0.0283
Gnomad4 SAS
AF:
0.227
Gnomad4 FIN
AF:
0.0810
Gnomad4 NFE
AF:
0.0994
Gnomad4 OTH
AF:
0.0670
Alfa
AF:
0.0438
Hom.:
34
Bravo
AF:
0.0684
Asia WGS
AF:
0.109
AC:
369
AN:
3368

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, criteria provided, single submitterclinical testingGeneDxMay 20, 2016This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
not provided Benign:1
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
CADD
Benign
16
DANN
Benign
0.83

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs146168804; hg19: chr4-3465073; API