dbSNP rs1716975: ULK4:p.Ile224Phe (chr3-41918514-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017886.4(ULK4):c.670A>T(p.Ile224Phe) 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. 16/21 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. I224V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ULK4
NM_017886.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.135

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]

ULK4 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.021968007).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ULK4	NM_017886.4 link	c.670A>T	p.Ile224Phe	missense_variant	Exon 7 of 37	ENST00000301831.9	NP_060356.2	Q96C45
ULK4	NM_001322500.2 link	c.670A>T	p.Ile224Phe	missense_variant	Exon 7 of 36		NP_001309429.1
ULK4	NM_001322501.2 link	c.-161A>T		5_prime_UTR_variant	Exon 7 of 36		NP_001309430.1
ULK4	NR_136342.2 link	n.806A>T		non_coding_transcript_exon_variant	Exon 7 of 35

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ULK4	ENST00000301831.9 link	c.670A>T	p.Ile224Phe	missense_variant	Exon 7 of 37	2	NM_017886.4	ENSP00000301831.4		Q96C45
ULK4	ENST00000420927.5 link	c.670A>T	p.Ile224Phe	missense_variant	Exon 7 of 18	1		ENSP00000412187.1		A0A0C4DG77

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1433092

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

711640

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

1.2

DANN

Benign

0.23

DEOGEN2

Benign

0.0017

T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0049

LIST_S2

Benign

0.55

T;T

M_CAP

Benign

0.0061

MetaRNN

Benign

0.022

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.53

N;.

PrimateAI

Benign

0.32

PROVEAN

Benign

1.6

N;N

REVEL

Benign

0.055

Sift

Benign

0.83

T;T

Sift4G

Benign

0.81

T;T

Polyphen

0.0

B;.

Vest4

0.054

MutPred

0.35

Gain of glycosylation at S223 (P = 0.0316);Gain of glycosylation at S223 (P = 0.0316);

MVP

0.15

MPC

0.048

ClinPred

0.015

GERP RS

-5.9

Varity_R

0.14

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over