1-162522489-T-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_175866.5(UHMK1):āc.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
NM_175866.5 missense
Scores
3
7
9
Clinical Significance
Conservation
PhyloP100: 7.01
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 |
---|---|---|---|---|---|---|---|---|
UHMK1 | NM_175866.5 | c.1199T>C | p.Val400Ala | missense_variant | 8/8 | ENST00000489294.2 | NP_787062.1 | |
UHMK1 | NM_001184763.1 | c.977T>C | p.Val326Ala | missense_variant | 8/8 | NP_001171692.1 | ||
UHMK1 | NM_144624.2 | c.*75T>C | 3_prime_UTR_variant | 7/7 | NP_653225.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
UHMK1 | ENST00000489294.2 | c.1199T>C | p.Val400Ala | missense_variant | 8/8 | 1 | NM_175866.5 | ENSP00000420270.1 | ||
UHMK1 | ENST00000538489.5 | c.*75T>C | 3_prime_UTR_variant | 7/7 | 1 | ENSP00000446416.1 | ||||
UHMK1 | ENST00000545294.5 | c.977T>C | p.Val326Ala | missense_variant | 8/8 | 2 | ENSP00000441226.1 | |||
UHMK1 | ENST00000282169.8 | n.1780T>C | non_coding_transcript_exon_variant | 7/7 | 2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251408Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135876
GnomAD3 exomes
AF:
AC:
1
AN:
251408
Hom.:
AF XY:
AC XY:
0
AN XY:
135876
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461876Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727238
GnomAD4 exome
AF:
AC:
2
AN:
1461876
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
727238
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ExAC
AF:
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 submitter | clinical testing | Ambry Genetics | Oct 17, 2023 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
.;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;L
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Pathogenic
D;D
Polyphen
0.29
.;B
Vest4
MutPred
0.43
.;Loss of ubiquitination at K397 (P = 0.0931);
MVP
MPC
0.85
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at