rs10494370

chr1-162499123-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_175866.5(UHMK1):c.269-832A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,180 control chromosomes in the GnomAD database, including 1,262 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (1262 hom., cov: 32)
• Consequence: UHMK1 NM_175866.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.514

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UHMK1	NM_175866.5	c.269-832A>G		intron_variant		ENST00000489294.2
UHMK1	NM_001184763.1	c.47-832A>G		intron_variant
UHMK1	NM_144624.2	c.269-832A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UHMK1	ENST00000489294.2	c.269-832A>G		intron_variant		1	NM_175866.5	P1
UHMK1	ENST00000538489.5	c.269-832A>G		intron_variant		1
UHMK1	ENST00000545294.5	c.47-832A>G		intron_variant		2
UHMK1	ENST00000282169.8	n.185-832A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18023 AN: 152062 Hom.: 1258 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.0884

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.0962

Gnomad OTH AF: 0.152

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.119 AC: 18047 AN: 152180 Hom.: 1262 Cov.: 32 AF XY: 0.120 AC XY: 8962 AN XY: 74416

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.267

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.0884

Gnomad4 NFE AF: 0.0963

Gnomad4 OTH AF: 0.152

Alfa AF: 0.112 Hom.: 1490

Bravo AF: 0.129

Asia WGS AF: 0.221 AC: 772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	2.3
Dann	Benign	0.59

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: rs10494370; hg19: chr1-162468913;