Variant 1-162498223-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_175866.5(UHMK1):c.223A>G(p.Lys75Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,176 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

UHMK1
NM_175866.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.49

Variant links:

Genes affected

UHMK1 (HGNC:19683): (U2AF homology motif kinase 1) The gene encodes a serine/threonine protein kinase that promotes cell cycle progression through G1 by phosphorylation of the cyclin-dependent kinase inhibitor 1B (p27Kip1), which causes nuclear export and degradation. The encoded protein is also thought to function in the adult nervous system and the gene has been associated with schizophrenia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

UHMK1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
UHMK1	NM_175866.5 linkuse as main transcript	c.223A>G	p.Lys75Glu	missense_variant	1/8	ENST00000489294.2
UHMK1	NM_144624.2 linkuse as main transcript	c.223A>G	p.Lys75Glu	missense_variant	1/7
UHMK1	NM_001184763.1 linkuse as main transcript	c.46+927A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UHMK1	ENST00000489294.2 linkuse as main transcript	c.223A>G	p.Lys75Glu	missense_variant	1/8	1	NM_175866.5	P1	Q8TAS1-1
UHMK1	ENST00000538489.5 linkuse as main transcript	c.223A>G	p.Lys75Glu	missense_variant	1/7	1			Q8TAS1-2
UHMK1	ENST00000545294.5 linkuse as main transcript	c.46+927A>G		intron_variant		2			Q8TAS1-3
UHMK1	ENST00000282169.8 linkuse as main transcript	n.139A>G		non_coding_transcript_exon_variant	1/7	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1457176

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724286

show subpopulations

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 21, 2021

The c.223A>G (p.K75E) alteration is located in exon 1 (coding exon 1) of the UHMK1 gene. This alteration results from a A to G substitution at nucleotide position 223, causing the lysine (K) at amino acid position 75 to be replaced by a glutamic acid (E). 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

Pathogenic

0.92

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.68

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.58

N;N

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.21

Sift

Benign

0.035

D;T

Sift4G

Benign

0.10

T;T

Polyphen

0.97

D;P

Vest4

0.70

MutPred

0.63

Loss of ubiquitination at K75 (P = 0.011);Loss of ubiquitination at K75 (P = 0.011);

MVP

0.35

MPC

0.75

ClinPred

0.96

GERP RS

4.9

Varity_R

0.48

gMVP

0.62

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over