3-41566050-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_017886.4(ULK4):c.3201G>A(p.Ser1067=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00554 in 1,613,564 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0057 (33 hom.)
• Consequence: ULK4 NM_017886.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.83

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 Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 3-41566050-C-T is Benign according to our data. Variant chr3-41566050-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 789277.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.83 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ULK4	NM_017886.4	c.3201G>A	p.Ser1067=	synonymous_variant	32/37	ENST00000301831.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ULK4	ENST00000301831.9	c.3201G>A	p.Ser1067=	synonymous_variant	32/37	2	NM_017886.4	P1

Frequencies

GnomAD3 genomes AF: 0.00371 AC: 564 AN: 151922 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00171

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.000663

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00641

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00445 AC: 1109 AN: 249194 Hom.: 6 AF XY: 0.00473 AC XY: 640 AN XY: 135206

Gnomad AFR exome AF: 0.000969

Gnomad AMR exome AF: 0.00180

Gnomad ASJ exome AF: 0.0118

Gnomad EAS exome AF: 0.0000557

Gnomad SAS exome AF: 0.00173

Gnomad FIN exome AF: 0.00125

Gnomad NFE exome AF: 0.00712

Gnomad OTH exome AF: 0.00448

GnomAD4 exome AF: 0.00573 AC: 8376 AN: 1461524 Hom.: 33 Cov.: 30 AF XY: 0.00574 AC XY: 4176 AN XY: 727050

Gnomad4 AFR exome AF: 0.000896

Gnomad4 AMR exome AF: 0.00195

Gnomad4 ASJ exome AF: 0.0116

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00160

Gnomad4 FIN exome AF: 0.00107

Gnomad4 NFE exome AF: 0.00671

Gnomad4 OTH exome AF: 0.00475

GnomAD4 genome AF: 0.00370 AC: 563 AN: 152040 Hom.: 0 Cov.: 32 AF XY: 0.00334 AC XY: 248 AN XY: 74302

Gnomad4 AFR AF: 0.00104

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.000663

Gnomad4 NFE AF: 0.00640

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00536 Hom.: 2

Bravo AF: 0.00404

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2023	ULK4: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Apr 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
Cadd	Benign	7.3
Dann	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs143473972; hg19: chr3-41607541;