chr3-41898501-T-G

Variant names:

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

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>C 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: 0.00001679
• 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=-0.75).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ULK4	NM_017886.4	c.1288-9A>C		intron_variant	Intron 13 of 36	ENST00000301831.9	NP_060356.2
ULK4	NM_001322500.2	c.1288-9A>C		intron_variant	Intron 13 of 35		NP_001309429.1
ULK4	NM_001322501.2	c.382-9A>C		intron_variant	Intron 12 of 35		NP_001309430.1
ULK4	NR_136342.2	n.1354-9A>C		intron_variant	Intron 12 of 34

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ULK4	ENST00000301831.9	c.1288-9A>C		intron_variant	Intron 13 of 36	2	NM_017886.4	ENSP00000301831.4
ULK4	ENST00000420927.5	c.1288-9A>C		intron_variant	Intron 13 of 17	1		ENSP00000412187.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1205434 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: 66876

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: 923844

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

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 12814

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.070
DANN	Benign	0.73
PhyloP100		-0.69

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000017
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.030		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;