Menu
GeneBe

17-4897991-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_153827.5(MINK1):​c.*704C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 145,204 control chromosomes in the GnomAD database, including 48,638 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.82 ( 48638 hom., cov: 23)
Exomes 𝑓: 0.76 ( 114 hom. )
Failed GnomAD Quality Control

Consequence

MINK1
NM_153827.5 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.238
Variant links:
Genes affected
CHRNE (HGNC:1966): (cholinergic receptor nicotinic epsilon subunit) Acetylcholine receptors at mature mammalian neuromuscular junctions are pentameric protein complexes composed of four subunits in the ratio of two alpha subunits to one beta, one epsilon, and one delta subunit. The acetylcholine receptor changes subunit composition shortly after birth when the epsilon subunit replaces the gamma subunit seen in embryonic receptors. Mutations in the epsilon subunit are associated with congenital myasthenic syndrome. [provided by RefSeq, Sep 2009]
MINK1 (HGNC:17565): (misshapen like kinase 1) This gene encodes a serine/threonine kinase belonging to the germinal center kinase (GCK) family. The protein is structurally similar to the kinases that are related to NIK and may belong to a distinct subfamily of NIK-related kinases within the GCK family. Studies of the mouse homolog indicate an up-regulation of expression in the course of postnatal mouse cerebral development and activation of the cJun N-terminal kinase (JNK) and the p38 pathways. [provided by RefSeq, Mar 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 17-4897991-C-T is Benign according to our data. Variant chr17-4897991-C-T is described in ClinVar as [Benign]. Clinvar id is 323958.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CHRNENM_000080.4 linkuse as main transcriptc.*745G>A 3_prime_UTR_variant 12/12 ENST00000649488.2
MINK1NM_153827.5 linkuse as main transcriptc.*704C>T 3_prime_UTR_variant 32/32 ENST00000355280.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MINK1ENST00000355280.11 linkuse as main transcriptc.*704C>T 3_prime_UTR_variant 32/321 NM_153827.5 A1Q8N4C8-1
CHRNEENST00000649488.2 linkuse as main transcriptc.*745G>A 3_prime_UTR_variant 12/12 NM_000080.4 P1

Frequencies

GnomAD3 genomes
AF:
0.818
AC:
118638
AN:
145086
Hom.:
48601
Cov.:
23
show subpopulations
Gnomad AFR
AF:
0.728
Gnomad AMI
AF:
0.949
Gnomad AMR
AF:
0.864
Gnomad ASJ
AF:
0.869
Gnomad EAS
AF:
0.742
Gnomad SAS
AF:
0.794
Gnomad FIN
AF:
0.829
Gnomad MID
AF:
0.856
Gnomad NFE
AF:
0.864
Gnomad OTH
AF:
0.847
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.765
AC:
283
AN:
370
Hom.:
114
Cov.:
0
AF XY:
0.776
AC XY:
132
AN XY:
170
show subpopulations
Gnomad4 AMR exome
AF:
0.850
Gnomad4 ASJ exome
AF:
1.00
Gnomad4 EAS exome
AF:
0.500
Gnomad4 SAS exome
AF:
0.792
Gnomad4 FIN exome
AF:
0.864
Gnomad4 NFE exome
AF:
0.752
Gnomad4 OTH exome
AF:
0.591
GnomAD4 genome
AF:
0.818
AC:
118733
AN:
145204
Hom.:
48638
Cov.:
23
AF XY:
0.817
AC XY:
57681
AN XY:
70630
show subpopulations
Gnomad4 AFR
AF:
0.728
Gnomad4 AMR
AF:
0.864
Gnomad4 ASJ
AF:
0.869
Gnomad4 EAS
AF:
0.742
Gnomad4 SAS
AF:
0.794
Gnomad4 FIN
AF:
0.829
Gnomad4 NFE
AF:
0.864
Gnomad4 OTH
AF:
0.847
Alfa
AF:
0.724
Hom.:
2595

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Congenital myasthenic syndrome Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
1.7
DANN
Benign
0.52
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.2

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: rs1053751; hg19: chr17-4801286; API