chr15-74839978-A-G

Variant names:

• chr15-74839978-A-G
• rs936229
• NM_001099436.4:c.696+256T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001099436.4(ULK3):​c.696+256T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 151,972 control chromosomes in the GnomAD database, including 34,270 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.67 (34270 hom., cov: 31)
• Consequence: ULK3 NM_001099436.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.946
• Publications: 28 publications found

Genes affected

ULK3 (HGNC:19703): (unc-51 like kinase 3) Enables protein serine/threonine kinase activity. Involved in several processes, including fibroblast activation; protein autophosphorylation; and regulation of smoothened signaling pathway. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099436.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ULK3	NM_001099436.4	MANE Select	c.696+256T>C		intron	N/A	NP_001092906.3
	ULK3	NM_001411082.1		c.729+256T>C		intron	N/A	NP_001398011.1
	ULK3	NM_001284364.3		c.696+256T>C		intron	N/A	NP_001271293.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ULK3	ENST00000440863.7	TSL:2 MANE Select	c.696+256T>C		intron	N/A	ENSP00000400312.2
	ULK3	ENST00000569437.5	TSL:1	c.696+256T>C		intron	N/A	ENSP00000456051.1
	ULK3	ENST00000566479.5	TSL:1	n.901+256T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.669 AC: 101562 AN: 151852 Hom.: 34242 Cov.: 31

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.710

Gnomad OTH AF: 0.662

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.669 AC: 101644 AN: 151972 Hom.: 34270 Cov.: 31 AF XY: 0.666 AC XY: 49460 AN XY: 74252

African (AFR) AF: 0.585 AC: 24252 AN: 41426

American (AMR) AF: 0.682 AC: 10428 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 2433 AN: 3470

East Asian (EAS) AF: 0.710 AC: 3648 AN: 5140

South Asian (SAS) AF: 0.675 AC: 3254 AN: 4818

European-Finnish (FIN) AF: 0.670 AC: 7094 AN: 10586

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.710 AC: 48224 AN: 67928

Other (OTH) AF: 0.664 AC: 1402 AN: 2112

Alfa AF: 0.699 Hom.: 53516

Bravo AF: 0.669

Asia WGS AF: 0.718 AC: 2497 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.5
DANN	Benign	0.72
PhyloP100		0.95
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs936229; hg19: chr15-75132319;