Genetic Variant UHMK1:p.Ala157Val (chr1-162500156-C-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_175866.5(UHMK1):c.470C>T(p.Ala157Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,614,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

UHMK1
NM_175866.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.06

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.846

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UHMK1	NM_175866.5 link	c.470C>T	p.Ala157Val	missense_variant	Exon 2 of 8	ENST00000489294.2	NP_787062.1	Q8TAS1-1
UHMK1	NM_001184763.1 link	c.248C>T	p.Ala83Val	missense_variant	Exon 2 of 8		NP_001171692.1	Q8TAS1-3
UHMK1	NM_144624.2 link	c.470C>T	p.Ala157Val	missense_variant	Exon 2 of 7		NP_653225.2	Q8TAS1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
UHMK1	ENST00000489294.2 link	c.470C>T	p.Ala157Val	missense_variant	Exon 2 of 8	1	NM_175866.5	ENSP00000420270.1	Q8TAS1-1
UHMK1	ENST00000538489.5 link	c.470C>T	p.Ala157Val	missense_variant	Exon 2 of 7	1		ENSP00000446416.1	Q8TAS1-2
UHMK1	ENST00000545294.5 link	c.248C>T	p.Ala83Val	missense_variant	Exon 2 of 8	2		ENSP00000441226.1	Q8TAS1-3
UHMK1	ENST00000282169.8 link	n.386C>T		non_coding_transcript_exon_variant	Exon 2 of 7	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251468

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.470C>T (p.A157V) alteration is located in exon 2 (coding exon 2) of the UHMK1 gene. This alteration results from a C to T substitution at nucleotide position 470, causing the alanine (A) at amino acid position 157 to be replaced by a valine (V). 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

0.99

BayesDel_addAF

Uncertain

0.073

BayesDel_noAF

Uncertain

-0.040

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.22

.;.;T

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

D;D;D

M_CAP

Benign

0.015

MetaRNN

Pathogenic

0.85

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

.;L;L

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.4

N;N;N

REVEL

Uncertain

0.32

Sift

Benign

0.081

T;T;T

Sift4G

Benign

0.31

T;T;T

Polyphen

1.0

.;D;D

Vest4

0.89

MutPred

0.72

.;Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);

MVP

0.56

MPC

1.0

ClinPred

0.67

GERP RS

5.7

Varity_R

0.12

gMVP

0.68

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over