17-4887675-A-G

Position:

• chr17-4887675-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.40

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 Likely_benign. Variant got -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/exons	MANE	Protein	UniProt
MINK1	NM_153827.5	c.1115A>G	p.Gln372Arg	missense_variant	12/32	ENST00000355280.11	NP_722549.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MINK1	ENST00000355280.11	c.1115A>G	p.Gln372Arg	missense_variant	12/32	1	NM_153827.5	ENSP00000347427.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000425 AC: 6 AN: 1413064 Hom.: 0 Cov.: 31 AF XY: 0.00000429 AC XY: 3 AN XY: 698962

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000551

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Nov 16, 2021

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	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.091	T;.;.
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	M;M;M
PrimateAI	Uncertain	0.72	T
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	D
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-4790970;