rs1052501

Positions:

• chr3-41883906-C-G
• chr3-41883906-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017886.4(ULK4):​c.1624G>C​(p.Ala542Pro) variant causes a missense 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A542T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ULK4 NM_017886.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07516155).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ULK4	NM_017886.4	c.1624G>C	p.Ala542Pro	missense_variant	17/37	ENST00000301831.9	NP_060356.2
ULK4	NM_001322500.2	c.1624G>C	p.Ala542Pro	missense_variant	17/36		NP_001309429.1
ULK4	NM_001322501.2	c.718G>C	p.Ala240Pro	missense_variant	16/36		NP_001309430.1
ULK4	NR_136342.2	n.1690G>C		non_coding_transcript_exon_variant	16/35

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ULK4	ENST00000301831.9	c.1624G>C	p.Ala542Pro	missense_variant	17/37	2	NM_017886.4	ENSP00000301831	P1
ULK4	ENST00000420927.5	c.1624G>C	p.Ala542Pro	missense_variant	17/18	1		ENSP00000412187

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1457292 Hom.: 0 Cov.: 42 AF XY: 0.00 AC XY: 0 AN XY: 725250

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	7.7
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0031	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.34	T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.075	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.024
Sift	Uncertain	0.024	D;D
Sift4G	Uncertain	0.033	D;D
Polyphen		0.13	B;.
Vest4		0.20
MutPred		0.21		Gain of disorder (P = 0.0503);Gain of disorder (P = 0.0503);
MVP		0.43
MPC		0.045
ClinPred		0.045	T
GERP RS		0.24
Varity_R		0.21
gMVP		0.40

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: rs1052501; hg19: chr3-41925398;