Genetic Variant MINK1:p.Gln372Arg (chr17-4887675-A-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_153827.5(MINK1):c.1115A>G(p.Gln372Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000425 in 1,413,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

MINK1
NM_153827.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.40

Publications

0 publications found

Variant links:

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]

MINK1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17252657).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MINK1	NM_153827.5 link	c.1115A>G	p.Gln372Arg	missense_variant	Exon 12 of 32	ENST00000355280.11	NP_722549.2	Q8N4C8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MINK1	ENST00000355280.11 link	c.1115A>G	p.Gln372Arg	missense_variant	Exon 12 of 32	1	NM_153827.5	ENSP00000347427.6		Q8N4C8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000425

AC:

AN:

1413064

Hom.:

Cov.:

AF XY:

0.00000429

AC XY:

AN XY:

698962

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31852

American (AMR)

AF:

0.00

AC:

AN:

36280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25290

East Asian (EAS)

AF:

0.00

AC:

AN:

36740

South Asian (SAS)

AF:

0.00

AC:

AN:

79952

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49886

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.00000551

AC:

AN:

1088746

Other (OTH)

AF:

0.00

AC:

AN:

58620

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 16, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1115A>G (p.Q372R) alteration is located in exon 12 (coding exon 12) of the MINK1 gene. This alteration results from a A to G substitution at nucleotide position 1115, causing the glutamine (Q) at amino acid position 372 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.067

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.091

T;.;.

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Benign

0.017

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.7

M;M;M

PhyloP100

4.4

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.0060

D;D;D

Sift4G

Benign

0.13

T;T;T

Polyphen

0.14

B;B;B

Vest4

0.33

MutPred

0.31

Gain of MoRF binding (P = 0.0224);Gain of MoRF binding (P = 0.0224);Gain of MoRF binding (P = 0.0224);

MVP

0.61

MPC

1.6

ClinPred

0.82

GERP RS

4.6

Varity_R

0.33

gMVP

0.65

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over