chr17-4890959-G-A

Variant names:

• chr17-4890959-G-A
• rs202107334
• NM_153827.5:c.1575G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_153827.5(MINK1):​c.1575G>A​(p.Glu525Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000712 in 1,403,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: MINK1 NM_153827.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.17
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP7: Synonymous conserved (PhyloP=3.17 with no splicing effect.

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.1575G>A	p.Glu525Glu	synonymous	Exon 15 of 32	NP_722549.2
	MINK1	NM_001024937.4		c.1575G>A	p.Glu525Glu	synonymous	Exon 15 of 32	NP_001020108.1	Q8N4C8-4
	MINK1	NM_170663.5		c.1575G>A	p.Glu525Glu	synonymous	Exon 15 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.1575G>A	p.Glu525Glu	synonymous	Exon 15 of 32	ENSP00000347427.6	Q8N4C8-1
	MINK1	ENST00000453408.7	TSL:1	c.1575G>A	p.Glu525Glu	synonymous	Exon 15 of 32	ENSP00000406487.3	Q8N4C8-4
	MINK1	ENST00000347992.11	TSL:1	c.1575G>A	p.Glu525Glu	synonymous	Exon 15 of 32	ENSP00000269296.7	Q8N4C8-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.12e-7 AC: 1 AN: 1403574 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 692654

African (AFR) AF: 0.00 AC: 0 AN: 31784

American (AMR) AF: 0.00 AC: 0 AN: 36084

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25212

East Asian (EAS) AF: 0.00 AC: 0 AN: 36092

South Asian (SAS) AF: 0.00 AC: 0 AN: 79364

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5710

European-Non Finnish (NFE) AF: 9.25e-7 AC: 1 AN: 1081482

Other (OTH) AF: 0.00 AC: 0 AN: 58274

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	5.5
DANN	Benign	0.51
PhyloP100		3.2

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

dbSNP: rs202107334; hg19: chr17-4794254;