chr17-4881229-G-C

Variant names:

• chr17-4881229-G-C
• NM_153827.5:c.278G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_153827.5(MINK1):​c.278G>C​(p.Ser93Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MINK1 NM_153827.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.94
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27727973).

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.278G>C	p.Ser93Thr	missense	Exon 4 of 32	NP_722549.2
	MINK1	NM_001024937.4		c.278G>C	p.Ser93Thr	missense	Exon 4 of 32	NP_001020108.1	Q8N4C8-4
	MINK1	NM_170663.5		c.278G>C	p.Ser93Thr	missense	Exon 4 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.278G>C	p.Ser93Thr	missense	Exon 4 of 32	ENSP00000347427.6	Q8N4C8-1
	MINK1	ENST00000453408.7	TSL:1	c.278G>C	p.Ser93Thr	missense	Exon 4 of 32	ENSP00000406487.3	Q8N4C8-4
	MINK1	ENST00000347992.11	TSL:1	c.278G>C	p.Ser93Thr	missense	Exon 4 of 32	ENSP00000269296.7	Q8N4C8-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

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	0.30
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.084	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	0.96	L
PhyloP100		4.9
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.28
Sift	Benign	0.11	T
Sift4G	Benign	0.29	T
Polyphen		0.96	D
Vest4		0.29
MutPred		0.32		Loss of glycosylation at S93 (P = 0.0462)
MVP		0.67
MPC		1.8
ClinPred		0.73	D
GERP RS		5.1
Varity_R		0.15
gMVP		0.88

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

hg19: chr17-4784524;