3-41398207-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_017886.4(ULK4):​c.3550G>A​(p.Val1184Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000242 in 1,612,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ULK4
NM_017886.4 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.12
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.30069077).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ULK4NM_017886.4 linkc.3550G>A p.Val1184Ile missense_variant Exon 35 of 37 ENST00000301831.9 NP_060356.2 Q96C45

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ULK4ENST00000301831.9 linkc.3550G>A p.Val1184Ile missense_variant Exon 35 of 37 2 NM_017886.4 ENSP00000301831.4 Q96C45

Frequencies

GnomAD3 genomes
AF:
0.0000790
AC:
12
AN:
151902
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000736
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.0000242
AC:
6
AN:
248392
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
134744
show subpopulations
Gnomad AFR exome
AF:
0.0000647
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000443
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000185
AC:
27
AN:
1460678
Hom.:
0
Cov.:
31
AF XY:
0.0000206
AC XY:
15
AN XY:
726618
show subpopulations
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:
0.0000187
Gnomad4 NFE exome
AF:
0.0000225
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000790
AC:
12
AN:
151902
Hom.:
0
Cov.:
32
AF XY:
0.0000944
AC XY:
7
AN XY:
74174
show subpopulations
Gnomad4 AFR
AF:
0.000145
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000736
Gnomad4 OTH
AF:
0.000479
Alfa
AF:
0.0000965
Hom.:
0
Bravo
AF:
0.0000491
ExAC
AF:
0.0000331
AC:
4

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 18, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.3550G>A (p.V1184I) alteration is located in exon 35 (coding exon 34) of the ULK4 gene. This alteration results from a G to A substitution at nucleotide position 3550, causing the valine (V) at amino acid position 1184 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0092
T
Eigen
Uncertain
0.35
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.85
D
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.30
T
MetaSVM
Benign
-0.69
T
MutationAssessor
Uncertain
2.3
M
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-0.38
N
REVEL
Benign
0.11
Sift
Benign
0.034
D
Sift4G
Benign
0.35
T
Polyphen
0.81
P
Vest4
0.37
MVP
0.48
MPC
0.13
ClinPred
0.41
T
GERP RS
5.7
Varity_R
0.11
gMVP
0.33

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs779277157; hg19: chr3-41439698; API