1-162520428-T-C

Variant names:

• chr1-162520428-T-C
• rs6427680
• NM_175866.5:c.1114-1976T>C

Variant summary

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

The NM_175866.5(UHMK1):​c.1114-1976T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 151,976 control chromosomes in the GnomAD database, including 15,906 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 0.46 (15906 hom., cov: 32)
• Consequence: UHMK1 NM_175866.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.269
• Publications: 9 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 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.1114-1976T>C		intron	N/A	NP_787062.1
	UHMK1	NM_001184763.1		c.892-1976T>C		intron	N/A	NP_001171692.1
	UHMK1	NM_144624.2		c.1025-1976T>C		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.1114-1976T>C		intron	N/A	ENSP00000420270.1
	UHMK1	ENST00000538489.5	TSL:1	c.1025-1976T>C		intron	N/A	ENSP00000446416.1
	UHMK1	ENST00000545294.5	TSL:2	c.892-1976T>C		intron	N/A	ENSP00000441226.1

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69359 AN: 151858 Hom.: 15903 Cov.: 32

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.457 AC: 69405 AN: 151976 Hom.: 15906 Cov.: 32 AF XY: 0.453 AC XY: 33632 AN XY: 74278

African (AFR) AF: 0.460 AC: 19070 AN: 41432

American (AMR) AF: 0.462 AC: 7056 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1347 AN: 3466

East Asian (EAS) AF: 0.474 AC: 2451 AN: 5172

South Asian (SAS) AF: 0.434 AC: 2092 AN: 4824

European-Finnish (FIN) AF: 0.450 AC: 4743 AN: 10538

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.458 AC: 31123 AN: 67954

Other (OTH) AF: 0.448 AC: 949 AN: 2116

Alfa AF: 0.459 Hom.: 20519

Bravo AF: 0.460

Asia WGS AF: 0.454 AC: 1579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.9
DANN	Benign	0.45
PhyloP100		0.27
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: rs6427680; hg19: chr1-162490218;