17-4890665-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153827.5(MINK1):c.1496G>C(p.Gly499Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,399,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MINK1 NM_153827.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.66

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1584644).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MINK1	NM_153827.5	c.1496G>C	p.Gly499Ala	missense_variant	14/32	ENST00000355280.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MINK1	ENST00000355280.11	c.1496G>C	p.Gly499Ala	missense_variant	14/32	1	NM_153827.5	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1399028 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 690094

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: 0.0000379

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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

Jun 18, 2021

The c.1496G>C (p.G499A) alteration is located in exon 14 (coding exon 14) of the MINK1 gene. This alteration results from a G to C substitution at nucleotide position 1496, causing the glycine (G) at amino acid position 499 to be replaced by an alanine (A). 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	0.074
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
Cadd	Benign	21
Dann	Benign	0.74
DEOGEN2	Benign	0.023	T;.;.
Eigen	Benign	0.10
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.79	T;T;T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.95	L;L;L
MutationTaster	Benign	0.81	N;N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.070	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.80	T;T;T
Sift4G	Benign	0.82	T;T;T
Polyphen		0.98	D;D;D
Vest4		0.073
MutPred		0.20		Loss of relative solvent accessibility (P = 0.0404);Loss of relative solvent accessibility (P = 0.0404);Loss of relative solvent accessibility (P = 0.0404);
MVP		0.62
MPC		0.18
ClinPred		0.20	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.024
gMVP		0.29

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: chr17-4793960;