chr17-4889741-G-A

Variant names:

• chr17-4889741-G-A
• rs1381598384
• NM_153827.5:c.1325G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153827.5(MINK1):​c.1325G>A​(p.Arg442Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000259 in 1,543,280 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: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: MINK1 NM_153827.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.93
• Publications: 0 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23772538).

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.1325G>A	p.Arg442Gln	missense	Exon 13 of 32	NP_722549.2
	MINK1	NM_001024937.4		c.1325G>A	p.Arg442Gln	missense	Exon 13 of 32	NP_001020108.1	Q8N4C8-4
	MINK1	NM_170663.5		c.1325G>A	p.Arg442Gln	missense	Exon 13 of 32	NP_733763.1	Q8N4C8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MINK1	ENST00000355280.11	TSL:1 MANE Select	c.1325G>A	p.Arg442Gln	missense	Exon 13 of 32	ENSP00000347427.6	Q8N4C8-1
	MINK1	ENST00000453408.7	TSL:1	c.1325G>A	p.Arg442Gln	missense	Exon 13 of 32	ENSP00000406487.3	Q8N4C8-4
	MINK1	ENST00000347992.11	TSL:1	c.1325G>A	p.Arg442Gln	missense	Exon 13 of 32	ENSP00000269296.7	Q8N4C8-3

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 151900 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000726

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

GnomAD4 exome AF: 7.19e-7 AC: 1 AN: 1391380 Hom.: 0 Cov.: 32 AF XY: 0.00000146 AC XY: 1 AN XY: 686720

African (AFR) AF: 0.00 AC: 0 AN: 31558

American (AMR) AF: 0.00 AC: 0 AN: 35730

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25094

East Asian (EAS) AF: 0.00 AC: 0 AN: 35830

South Asian (SAS) AF: 0.00 AC: 0 AN: 79282

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42498

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4102

European-Non Finnish (NFE) AF: 9.26e-7 AC: 1 AN: 1079480

Other (OTH) AF: 0.00 AC: 0 AN: 57806

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 151900 Hom.: 0 Cov.: 31 AF XY: 0.0000270 AC XY: 2 AN XY: 74188

African (AFR) AF: 0.0000726 AC: 3 AN: 41328

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67898

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		9.9
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.091
Sift	Uncertain	0.027	D
Sift4G	Benign	0.10	T
Polyphen		0.98	D
Vest4		0.20
MutPred		0.23		Loss of MoRF binding (P = 0.0483)
MVP		0.52
MPC		1.9
ClinPred		0.94	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.16
Mutation Taster		=77/23	polymorphism

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

Other links and lift over

dbSNP: rs1381598384; hg19: chr17-4793036;