Variant 17-4897899-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_153827.5(MINK1):c.*612T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 145,814 control chromosomes in the GnomAD database, including 9,519 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.36 ( 9494 hom., cov: 24)

Exomes 𝑓: 0.26 ( 25 hom. )

Consequence

MINK1
NM_153827.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.22

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]

CHRNE links:

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]

MINK1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 17-4897899-T-C is Benign according to our data. Variant chr17-4897899-T-C is described in ClinVar as [Benign]. Clinvar id is 323951.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-4897899-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNE	NM_000080.4 linkuse as main transcript	c.*837A>G		3_prime_UTR_variant	12/12	ENST00000649488.2
MINK1	NM_153827.5 linkuse as main transcript	c.*612T>C		3_prime_UTR_variant	32/32	ENST00000355280.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MINK1	ENST00000355280.11 linkuse as main transcript	c.*612T>C		3_prime_UTR_variant	32/32	1	NM_153827.5	A1	Q8N4C8-1
CHRNE	ENST00000649488.2 linkuse as main transcript	c.*837A>G		3_prime_UTR_variant	12/12		NM_000080.4	P1

Frequencies

GnomAD3 genomes

AF:

0.356

AC:

51636

AN:

145208

Hom.:

9507

Cov.:

show subpopulations

Gnomad AFR

AF:

0.313

Gnomad AMI

AF:

0.300

Gnomad AMR

AF:

0.372

Gnomad ASJ

AF:

0.437

Gnomad EAS

AF:

0.612

Gnomad SAS

AF:

0.631

Gnomad FIN

AF:

0.349

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.336

Gnomad OTH

AF:

0.367

GnomAD4 exome

AF:

0.262

AC:

128

AN:

488

Hom.:

Cov.:

AF XY:

0.238

AC XY:

AN XY:

256

show subpopulations

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.417

Gnomad4 FIN exome

AF:

0.257

Gnomad4 NFE exome

AF:

0.250

Gnomad4 OTH exome

AF:

0.250

GnomAD4 genome

AF:

0.355

AC:

51642

AN:

145326

Hom.:

9494

Cov.:

AF XY:

0.363

AC XY:

25616

AN XY:

70478

show subpopulations

Gnomad4 AFR

AF:

0.313

Gnomad4 AMR

AF:

0.371

Gnomad4 ASJ

AF:

0.437

Gnomad4 EAS

AF:

0.613

Gnomad4 SAS

AF:

0.630

Gnomad4 FIN

AF:

0.349

Gnomad4 NFE

AF:

0.336

Gnomad4 OTH

AF:

0.365

Alfa

AF:

0.302

Hom.:

2640

Bravo

AF:

0.343

Asia WGS

AF:

0.570

AC:

1980

AN:

3478

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 submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This 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

-0.55

CADD

Benign

DANN

Benign

0.51

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over