dbSNP rs1246962429: MINK1:p.Pro4Ala (chr17-4833593-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_153827.5(MINK1):c.10C>G(p.Pro4Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000533 in 1,500,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P4S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000030 ( 0 hom. )

Consequence

MINK1
NM_153827.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.82

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15073901).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MINK1	NM_153827.5 link	c.10C>G	p.Pro4Ala	missense_variant	Exon 1 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.10C>G	p.Pro4Ala	missense_variant	Exon 1 of 32	1	NM_153827.5	ENSP00000347427.6		Q8N4C8-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

96820

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000297

AC:

AN:

1348166

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

664854

show subpopulations

African (AFR)

AF:

0.000146

AC:

AN:

27464

American (AMR)

AF:

0.00

AC:

AN:

32198

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23944

East Asian (EAS)

AF:

0.00

AC:

AN:

30100

South Asian (SAS)

AF:

0.00

AC:

AN:

75734

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35050

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4290

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1063196

Other (OTH)

AF:

0.00

AC:

AN:

56190

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.0000965

AC:

AN:

41448

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68002

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.052

T;.;.

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.84

T;T;T

M_CAP

Pathogenic

0.62

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.20

N;N;N

PhyloP100

1.8

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.10

Sift

Benign

0.071

T;T;T

Sift4G

Benign

0.14

T;T;T

Polyphen

0.0070

B;B;B

Vest4

0.28

MutPred

0.18

Loss of disorder (P = 0.1916);Loss of disorder (P = 0.1916);Loss of disorder (P = 0.1916);

MVP

0.50

MPC

2.1

ClinPred

0.39

GERP RS

1.4

PromoterAI

-0.00010

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.075

gMVP

0.49

Mutation Taster

=89/11

polymorphism

(source)

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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rs1246962429

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over