1-162498171-G-T

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_175866.5(UHMK1):c.171G>T(p.Leu57Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,613,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

UHMK1
NM_175866.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0820

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0464665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UHMK1	NM_175866.5 link	c.171G>T	p.Leu57Phe	missense_variant	Exon 1 of 8	ENST00000489294.2	NP_787062.1	Q8TAS1-1
UHMK1	NM_144624.2 link	c.171G>T	p.Leu57Phe	missense_variant	Exon 1 of 7		NP_653225.2	Q8TAS1-2
UHMK1	NM_001184763.1 link	c.46+875G>T		intron_variant	Intron 1 of 7		NP_001171692.1	Q8TAS1-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
UHMK1	ENST00000489294.2 link	c.171G>T	p.Leu57Phe	missense_variant	Exon 1 of 8	1	NM_175866.5	ENSP00000420270.1	Q8TAS1-1
UHMK1	ENST00000538489.5 link	c.171G>T	p.Leu57Phe	missense_variant	Exon 1 of 7	1		ENSP00000446416.1	Q8TAS1-2
UHMK1	ENST00000545294.5 link	c.46+875G>T		intron_variant	Intron 1 of 7	2		ENSP00000441226.1	Q8TAS1-3
UHMK1	ENST00000282169.8 link	n.87G>T		non_coding_transcript_exon_variant	Exon 1 of 7	2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000163

AC:

AN:

245790

Hom.:

AF XY:

0.0000895

AC XY:

AN XY:

134072

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00114

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000905

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000322

AC:

AN:

1460768

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

726646

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000873

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:

0.00000630

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 27, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.171G>T (p.L57F) alteration is located in exon 1 (coding exon 1) of the UHMK1 gene. This alteration results from a G to T substitution at nucleotide position 171, causing the leucine (L) at amino acid position 57 to be replaced by a phenylalanine (F). 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

0.12

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

.;T

Eigen

Benign

0.070

Eigen_PC

Benign

0.039

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.79

T;T

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.046

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.3

L;L

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.10

Sift

Benign

0.15

T;T

Sift4G

Benign

0.22

T;T

Polyphen

0.90

P;P

Vest4

0.23

MutPred

0.43

Loss of ubiquitination at K54 (P = 0.069);Loss of ubiquitination at K54 (P = 0.069);

MVP

0.37

MPC

0.64

ClinPred

0.13

GERP RS

0.92

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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