NM_175866.5:c.849-2145A>G

Variant names:

• chr1-162510355-A-G
• rs7513662
• NM_175866.5:c.849-2145A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_175866.5(UHMK1):​c.849-2145A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 152,134 control chromosomes in the GnomAD database, including 6,033 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 0.25 (6033 hom., cov: 32)
• Consequence: UHMK1 NM_175866.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.606
• Publications: 11 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UHMK1	NM_175866.5	MANE Select	c.849-2145A>G		intron	N/A	NP_787062.1
	UHMK1	NM_001184763.1		c.627-2145A>G		intron	N/A	NP_001171692.1
	UHMK1	NM_144624.2		c.849-2145A>G		intron	N/A	NP_653225.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UHMK1	ENST00000489294.2	TSL:1 MANE Select	c.849-2145A>G		intron	N/A	ENSP00000420270.1
	UHMK1	ENST00000538489.5	TSL:1	c.849-2145A>G		intron	N/A	ENSP00000446416.1
	UHMK1	ENST00000545294.5	TSL:2	c.627-2145A>G		intron	N/A	ENSP00000441226.1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38473 AN: 152020 Hom.: 6034 Cov.: 32

Gnomad AFR AF: 0.0712

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.253 AC: 38473 AN: 152134 Hom.: 6033 Cov.: 32 AF XY: 0.251 AC XY: 18689 AN XY: 74350

African (AFR) AF: 0.0710 AC: 2950 AN: 41546

American (AMR) AF: 0.323 AC: 4931 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 975 AN: 3470

East Asian (EAS) AF: 0.212 AC: 1097 AN: 5164

South Asian (SAS) AF: 0.225 AC: 1084 AN: 4826

European-Finnish (FIN) AF: 0.350 AC: 3695 AN: 10562

Middle Eastern (MID) AF: 0.161 AC: 47 AN: 292

European-Non Finnish (NFE) AF: 0.335 AC: 22783 AN: 67978

Other (OTH) AF: 0.261 AC: 552 AN: 2114

Alfa AF: 0.270 Hom.: 6602

Bravo AF: 0.246

Asia WGS AF: 0.215 AC: 750 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.45
DANN	Benign	0.40
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7513662; hg19: chr1-162480145;