1-162522489-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_175866.5(UHMK1):ā€‹c.1199T>Cā€‹(p.Val400Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

UHMK1
NM_175866.5 missense

Scores

3
7
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.01
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3020361).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
UHMK1NM_175866.5 linkuse as main transcriptc.1199T>C p.Val400Ala missense_variant 8/8 ENST00000489294.2 NP_787062.1 Q8TAS1-1
UHMK1NM_001184763.1 linkuse as main transcriptc.977T>C p.Val326Ala missense_variant 8/8 NP_001171692.1 Q8TAS1-3
UHMK1NM_144624.2 linkuse as main transcriptc.*75T>C 3_prime_UTR_variant 7/7 NP_653225.2 Q8TAS1-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
UHMK1ENST00000489294.2 linkuse as main transcriptc.1199T>C p.Val400Ala missense_variant 8/81 NM_175866.5 ENSP00000420270.1 Q8TAS1-1
UHMK1ENST00000538489.5 linkuse as main transcriptc.*75T>C 3_prime_UTR_variant 7/71 ENSP00000446416.1 Q8TAS1-2
UHMK1ENST00000545294.5 linkuse as main transcriptc.977T>C p.Val326Ala missense_variant 8/82 ENSP00000441226.1 Q8TAS1-3
UHMK1ENST00000282169.8 linkuse as main transcriptn.1780T>C non_coding_transcript_exon_variant 7/72

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251408
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135876
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.00000137
AC:
2
AN:
1461876
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727238
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:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsOct 17, 2023The c.1199T>C (p.V400A) alteration is located in exon 8 (coding exon 8) of the UHMK1 gene. This alteration results from a T to C substitution at nucleotide position 1199, causing the valine (V) at amino acid position 400 to be replaced by an alanine (A). 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
0.87
BayesDel_addAF
Benign
-0.011
T
BayesDel_noAF
Benign
-0.16
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.55
.;D
Eigen
Uncertain
0.31
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.84
T;T
M_CAP
Benign
0.079
D
MetaRNN
Benign
0.30
T;T
MetaSVM
Benign
-0.54
T
MutationAssessor
Benign
1.5
.;L
PrimateAI
Uncertain
0.72
T
PROVEAN
Benign
-2.1
N;N
REVEL
Uncertain
0.30
Sift
Uncertain
0.0060
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.29
.;B
Vest4
0.47
MutPred
0.43
.;Loss of ubiquitination at K397 (P = 0.0931);
MVP
0.34
MPC
0.85
ClinPred
0.75
D
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.16
gMVP
0.64

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.

Other links and lift over

dbSNP: rs781750691; hg19: chr1-162492279; API