NM_153827.5:c.*706A>C

Variant names:

• chr17-4897993-A-C
• rs1053754
• NM_153827.5:c.*706A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_153827.5(MINK1):​c.*706A>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 0.544 in 139,842 control chromosomes in the GnomAD database, including 22,763 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (22763 hom., cov: 23)
  • Exomes 𝑓: 0.30 (17 hom.)
  • Failed GnomAD Quality Control
• Consequence: MINK1 NM_153827.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.779
• Publications: 10 publications found

Genes affected

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]

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 Gene-Disease associations (from GenCC):

• congenital myasthenic syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: Illumina
• congenital myasthenic syndrome 4A

  Inheritance: AD, AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• congenital myasthenic syndrome 4B

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• congenital myasthenic syndrome 4C

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
• postsynaptic congenital myasthenic syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 17-4897993-A-C is Benign according to our data. Variant chr17-4897993-A-C is described in ClinVar as Benign. ClinVar VariationId is 323959.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153827.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MINK1	NM_153827.5	MANE Select	c.*706A>C		3_prime_UTR	Exon 32 of 32	NP_722549.2
	CHRNE	NM_000080.4	MANE Select	c.*743T>G		3_prime_UTR	Exon 12 of 12	NP_000071.1	Q04844
	MINK1	NM_001024937.4		c.*706A>C		3_prime_UTR	Exon 32 of 32	NP_001020108.1	Q8N4C8-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MINK1	ENST00000355280.11	TSL:1 MANE Select	c.*706A>C		3_prime_UTR	Exon 32 of 32	ENSP00000347427.6	Q8N4C8-1
	CHRNE	ENST00000649488.2	MANE Select	c.*743T>G		3_prime_UTR	Exon 12 of 12	ENSP00000497829.1	Q04844
	MINK1	ENST00000347992.11	TSL:1	c.*706A>C		3_prime_UTR	Exon 32 of 32	ENSP00000269296.7	Q8N4C8-3

Frequencies

GnomAD3 genomes AF: 0.544 AC: 76053 AN: 139740 Hom.: 22754 Cov.: 23

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.575

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.570

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.295 AC: 108 AN: 366 Hom.: 17 Cov.: 0 AF XY: 0.256 AC XY: 43 AN XY: 168

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.114 AC: 5 AN: 44

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AF: 0.0714 AC: 3 AN: 42

European-Finnish (FIN) AF: 0.458 AC: 11 AN: 24

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.350 AC: 82 AN: 234

Other (OTH) AF: 0.500 AC: 7 AN: 14

GnomAD4 genome AF: 0.544 AC: 76092 AN: 139842 Hom.: 22763 Cov.: 23 AF XY: 0.535 AC XY: 36256 AN XY: 67748

African (AFR) AF: 0.274 AC: 9920 AN: 36220

American (AMR) AF: 0.554 AC: 7931 AN: 14314

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2119 AN: 3356

East Asian (EAS) AF: 0.193 AC: 814 AN: 4224

South Asian (SAS) AF: 0.460 AC: 1944 AN: 4224

European-Finnish (FIN) AF: 0.644 AC: 5850 AN: 9078

Middle Eastern (MID) AF: 0.588 AC: 160 AN: 272

European-Non Finnish (NFE) AF: 0.698 AC: 45555 AN: 65300

Other (OTH) AF: 0.571 AC: 1129 AN: 1976

Alfa AF: 0.578 Hom.: 31391

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Congenital myasthenic syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.84
DANN	Benign	0.53
PhyloP100		-0.78
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1053754; hg19: chr17-4801288;