chr17-4833589-C-T

Variant names:

• chr17-4833589-C-T
• rs375578873
• NM_153827.5:c.6C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_153827.5(MINK1):​c.6C>T​(p.Gly2Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000488 in 1,499,444 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0028 (2 hom., cov: 31)
  • Exomes 𝑓: 0.00022 (0 hom.)
• Consequence: MINK1 NM_153827.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.256
• 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP6: Variant 17-4833589-C-T is Benign according to our data. Variant chr17-4833589-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2647272.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.256 with no splicing effect.
• BS2: High AC in GnomAd4 at 432 AD gene.

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.6C>T	p.Gly2Gly	synonymous	Exon 1 of 32	NP_722549.2
	MINK1	NM_001024937.4		c.6C>T	p.Gly2Gly	synonymous	Exon 1 of 32	NP_001020108.1	Q8N4C8-4
	MINK1	NM_170663.5		c.6C>T	p.Gly2Gly	synonymous	Exon 1 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.6C>T	p.Gly2Gly	synonymous	Exon 1 of 32	ENSP00000347427.6	Q8N4C8-1
	MINK1	ENST00000453408.7	TSL:1	c.6C>T	p.Gly2Gly	synonymous	Exon 1 of 32	ENSP00000406487.3	Q8N4C8-4
	MINK1	ENST00000347992.11	TSL:1	c.6C>T	p.Gly2Gly	synonymous	Exon 1 of 32	ENSP00000269296.7	Q8N4C8-3

Frequencies

GnomAD3 genomes AF: 0.00282 AC: 429 AN: 152118 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.00937

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

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: 0.0000441

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000416 AC: 40 AN: 96060 AF XY: 0.000277

Gnomad AFR exome AF: 0.0117

Gnomad AMR exome AF: 0.000851

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00104

GnomAD4 exome AF: 0.000223 AC: 300 AN: 1347210 Hom.: 0 Cov.: 31 AF XY: 0.000169 AC XY: 112 AN XY: 664348

African (AFR) AF: 0.00827 AC: 227 AN: 27434

American (AMR) AF: 0.000905 AC: 29 AN: 32050

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23908

East Asian (EAS) AF: 0.00 AC: 0 AN: 30040

South Asian (SAS) AF: 0.00 AC: 0 AN: 75640

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35036

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4300

European-Non Finnish (NFE) AF: 0.00000659 AC: 7 AN: 1062652

Other (OTH) AF: 0.000659 AC: 37 AN: 56150

GnomAD4 genome AF: 0.00284 AC: 432 AN: 152234 Hom.: 2 Cov.: 31 AF XY: 0.00266 AC XY: 198 AN XY: 74446

African (AFR) AF: 0.00941 AC: 391 AN: 41552

American (AMR) AF: 0.00216 AC: 33 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67986

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00170 Hom.: 0

Bravo AF: 0.00336

Asia WGS AF: 0.00116 AC: 4 AN: 3474

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	15
DANN	Benign	0.95
PhyloP100		0.26
PromoterAI		-0.029	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs375578873; hg19: chr17-4736884;