chr3-41954644-T-C

Variant names:

• chr3-41954644-T-C
• rs2272007
• NM_017886.4:c.116A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017886.4(ULK4):​c.116A>G​(p.Lys39Arg) variant causes a missense change. The variant allele was found at a frequency of 0.806 in 1,613,112 control chromosomes in the GnomAD database, including 533,999 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.68 (39046 hom., cov: 31)
  • Exomes 𝑓: 0.82 (494953 hom.)
• Consequence: ULK4 NM_017886.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.83
• Publications: 85 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.5337359E-6).
• BP6: Variant 3-41954644-T-C is Benign according to our data. Variant chr3-41954644-T-C is described in ClinVar as Benign. ClinVar VariationId is 403591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017886.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ULK4	NM_017886.4	MANE Select	c.116A>G	p.Lys39Arg	missense	Exon 2 of 37	NP_060356.2	Q96C45
	ULK4	NM_001322500.2		c.116A>G	p.Lys39Arg	missense	Exon 2 of 36	NP_001309429.1
	ULK4	NM_001322501.2		c.-715A>G		5_prime_UTR	Exon 2 of 36	NP_001309430.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ULK4	ENST00000301831.9	TSL:2 MANE Select	c.116A>G	p.Lys39Arg	missense	Exon 2 of 37	ENSP00000301831.4	Q96C45
	ULK4	ENST00000420927.5	TSL:1	c.116A>G	p.Lys39Arg	missense	Exon 2 of 18	ENSP00000412187.1	A0A0C4DG77
	ULK4	ENST00000951851.1		c.116A>G	p.Lys39Arg	missense	Exon 2 of 37	ENSP00000621910.1

Frequencies

GnomAD3 genomes AF: 0.682 AC: 103699 AN: 151942 Hom.: 39029 Cov.: 31

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.809

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.775

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.828

Gnomad OTH AF: 0.700

GnomAD2 exomes AF: 0.794 AC: 197721 AN: 249110 AF XY: 0.799

Gnomad AFR exome AF: 0.328

Gnomad AMR exome AF: 0.857

Gnomad ASJ exome AF: 0.817

Gnomad EAS exome AF: 0.818

Gnomad FIN exome AF: 0.777

Gnomad NFE exome AF: 0.827

Gnomad OTH exome AF: 0.797

GnomAD4 exome AF: 0.819 AC: 1196390 AN: 1461052 Hom.: 494953 Cov.: 48 AF XY: 0.820 AC XY: 596273 AN XY: 726880

African (AFR) AF: 0.311 AC: 10410 AN: 33444

American (AMR) AF: 0.852 AC: 38006 AN: 44606

Ashkenazi Jewish (ASJ) AF: 0.812 AC: 21211 AN: 26114

East Asian (EAS) AF: 0.853 AC: 33852 AN: 39680

South Asian (SAS) AF: 0.822 AC: 70794 AN: 86132

European-Finnish (FIN) AF: 0.786 AC: 41970 AN: 53392

Middle Eastern (MID) AF: 0.648 AC: 3736 AN: 5762

European-Non Finnish (NFE) AF: 0.836 AC: 928764 AN: 1111550

Other (OTH) AF: 0.789 AC: 47647 AN: 60372

GnomAD4 genome AF: 0.682 AC: 103732 AN: 152060 Hom.: 39046 Cov.: 31 AF XY: 0.684 AC XY: 50808 AN XY: 74306

African (AFR) AF: 0.333 AC: 13818 AN: 41462

American (AMR) AF: 0.783 AC: 11955 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.809 AC: 2805 AN: 3468

East Asian (EAS) AF: 0.834 AC: 4301 AN: 5154

South Asian (SAS) AF: 0.820 AC: 3955 AN: 4826

European-Finnish (FIN) AF: 0.775 AC: 8204 AN: 10584

Middle Eastern (MID) AF: 0.606 AC: 177 AN: 292

European-Non Finnish (NFE) AF: 0.828 AC: 56322 AN: 67984

Other (OTH) AF: 0.702 AC: 1480 AN: 2108

Alfa AF: 0.782 Hom.: 223522

Bravo AF: 0.668

TwinsUK AF: 0.831 AC: 3083

ALSPAC AF: 0.839 AC: 3234

ESP6500AA AF: 0.358 AC: 1352

ESP6500EA AF: 0.825 AC: 6790

ExAC AF: 0.786 AC: 94999

Asia WGS AF: 0.805 AC: 2801 AN: 3478

EpiCase AF: 0.810

EpiControl AF: 0.813

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	20
DANN	Benign	0.90
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.81	T
MetaRNN	Benign	0.0000015	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.030	N
PhyloP100		3.8
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.066
Sift	Benign	0.32	T
Sift4G	Benign	0.40	T
Polyphen		0.20	B
Vest4		0.087
MPC		0.053
ClinPred		0.015	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.29
gMVP		0.38
Mutation Taster		=90/10	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2272007; hg19: chr3-41996136; COSMIC: COSV57209557; COSMIC: COSV57209557;