NM_017886.4:c.1288-9A>G

Variant names:

• chr3-41898501-T-C
• rs1625226
• NM_017886.4:c.1288-9A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017886.4(ULK4):​c.1288-9A>G variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ULK4 NM_017886.4 intron
• Scores: Splicing: ADA: 0.0001526
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.694
• Publications: 8 publications found

Genes affected

ULK4 (HGNC:15784): (unc-51 like kinase 4) This gene encodes a member of the unc-51-like serine/threonine kinase (STK) family. Members of this protein family play a role in neuronal growth and endocytosis. The encoded protein is likely involved in neurite branching, neurite elongation and neuronal migration. Genome-wide association studies (GWAS) indicate an association of variations in this gene with blood pressure and hypertension. Sequence variations in this gene may also be be associated with psychiatric disorders, including schizophrenia and bipolar disorder. Pseudogenes associated with this gene have been identified and are located on chromosome 15. [provided by RefSeq, Jul 2016]

ULK4 Gene-Disease associations (from GenCC):

• prostate cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017886.4. 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
	ULK4	NM_017886.4	MANE Select	c.1288-9A>G		intron	N/A	NP_060356.2
	ULK4	NM_001322500.2		c.1288-9A>G		intron	N/A	NP_001309429.1
	ULK4	NM_001322501.2		c.382-9A>G		intron	N/A	NP_001309430.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ULK4	ENST00000301831.9	TSL:2 MANE Select	c.1288-9A>G		intron	N/A	ENSP00000301831.4
	ULK4	ENST00000420927.5	TSL:1	c.1288-9A>G		intron	N/A	ENSP00000412187.1
	ULK4	ENST00000951851.1		c.1285-9A>G		intron	N/A	ENSP00000621910.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1205438 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 600212

African (AFR) AF: 0.00 AC: 0 AN: 28666

American (AMR) AF: 0.00 AC: 0 AN: 32370

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20838

East Asian (EAS) AF: 0.00 AC: 0 AN: 32580

South Asian (SAS) AF: 0.00 AC: 0 AN: 66878

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45660

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5032

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 923846

Other (OTH) AF: 0.00 AC: 0 AN: 49568

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.067
DANN	Benign	0.88
PhyloP100		-0.69

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00015
dbscSNV1_RF	Benign	0.026
SpliceAI score (max)		0.020		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: rs1625226; hg19: chr3-41939993;