17-4881229-G-C

Position:

• chr17-4881229-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MINK1	NM_153827.5	c.278G>C	p.Ser93Thr	missense_variant	4/32	ENST00000355280.11	NP_722549.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MINK1	ENST00000355280.11	c.278G>C	p.Ser93Thr	missense_variant	4/32	1	NM_153827.5	ENSP00000347427.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 20, 2023

The c.278G>C (p.S93T) alteration is located in exon 4 (coding exon 4) of the MINK1 gene. This alteration results from a G to C substitution at nucleotide position 278, causing the serine (S) at amino acid position 93 to be replaced by a threonine (T). 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	0.30
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;T;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	0.96	L;L;L
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-2.1	N;N;N
REVEL	Benign	0.28
Sift	Benign	0.11	T;T;T
Sift4G	Benign	0.29	T;T;T
Polyphen		0.96	D;P;P
Vest4		0.29
MutPred		0.32		Loss of glycosylation at S93 (P = 0.0462);Loss of glycosylation at S93 (P = 0.0462);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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-4784524;