1-162498171-G-C

Variant names:

• chr1-162498171-G-C
• NM_175866.5:c.171G>C
• UHMK1 p.Leu57Phe

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_175866.5(UHMK1):​c.171G>C​(p.Leu57Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: UHMK1 NM_175866.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0820
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 0.84423 (below the threshold of 3.09). Trascript score misZ: 1.1318 (below the threshold of 3.09).
• BP4: Computational evidence support a benign effect (MetaRNN=0.21549907).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175866.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UHMK1	NM_175866.5	MANE Select	c.171G>C	p.Leu57Phe	missense	Exon 1 of 8	NP_787062.1	Q8TAS1-1
	UHMK1	NM_144624.2		c.171G>C	p.Leu57Phe	missense	Exon 1 of 7	NP_653225.2	Q8TAS1-2
	UHMK1	NM_001184763.1		c.46+875G>C		intron	N/A	NP_001171692.1	Q8TAS1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UHMK1	ENST00000489294.2	TSL:1 MANE Select	c.171G>C	p.Leu57Phe	missense	Exon 1 of 8	ENSP00000420270.1	Q8TAS1-1
	UHMK1	ENST00000538489.5	TSL:1	c.171G>C	p.Leu57Phe	missense	Exon 1 of 7	ENSP00000446416.1	Q8TAS1-2
	UHMK1	ENST00000874790.1		c.171G>C	p.Leu57Phe	missense	Exon 1 of 8	ENSP00000544849.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Benign	0.070
Eigen_PC	Benign	0.039
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.79	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.3	L
PhyloP100		-0.082
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.10
Sift	Benign	0.15	T
Sift4G	Benign	0.22	T
PromoterAI		-0.11	Neutral
Varity_R		0.11
gMVP		0.26
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-162467961;