1-162499991-C-G

Variant names:

• chr1-162499991-C-G
• rs1157424991
• NM_175866.5:c.305C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_175866.5(UHMK1):​c.305C>G​(p.Pro102Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: UHMK1 NM_175866.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.89

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11089915).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UHMK1	NM_175866.5	c.305C>G	p.Pro102Arg	missense_variant	Exon 2 of 8	ENST00000489294.2	NP_787062.1
UHMK1	NM_001184763.1	c.83C>G	p.Pro28Arg	missense_variant	Exon 2 of 8		NP_001171692.1
UHMK1	NM_144624.2	c.305C>G	p.Pro102Arg	missense_variant	Exon 2 of 7		NP_653225.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UHMK1	ENST00000489294.2	c.305C>G	p.Pro102Arg	missense_variant	Exon 2 of 8	1	NM_175866.5	ENSP00000420270.1
UHMK1	ENST00000538489.5	c.305C>G	p.Pro102Arg	missense_variant	Exon 2 of 7	1		ENSP00000446416.1
UHMK1	ENST00000545294.5	c.83C>G	p.Pro28Arg	missense_variant	Exon 2 of 8	2		ENSP00000441226.1
UHMK1	ENST00000282169.8	n.221C>G		non_coding_transcript_exon_variant	Exon 2 of 7	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000130 AC: 19 AN: 1461862 Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 10 AN XY: 727230

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: 0.0000171

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.305C>G (p.P102R) alteration is located in exon 2 (coding exon 2) of the UHMK1 gene. This alteration results from a C to G substitution at nucleotide position 305, causing the proline (P) at amino acid position 102 to be replaced by an arginine (R). 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	0.11
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Benign	0.93
DEOGEN2	Benign	0.14	.;.;T
Eigen	Benign	-0.036
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	.;L;L
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.45	N;N;N
REVEL	Benign	0.076
Sift	Benign	0.19	T;T;T
Sift4G	Benign	0.49	T;T;T
Polyphen		0.092, 0.11	.;B;B
Vest4		0.31
MVP		0.093
MPC		0.35
ClinPred		0.19	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.33

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

Other links and lift over

dbSNP: rs1157424991; hg19: chr1-162469781;