chr16-74906468-C-A

Variant names:

• chr16-74906468-C-A
• rs11149780
• NM_030581.4:c.1713-2368G>T

Variant summary

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

The NM_030581.4(WDR59):​c.1713-2368G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 151,614 control chromosomes in the GnomAD database, including 22,067 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 0.50 (22067 hom., cov: 29)
• Consequence: WDR59 NM_030581.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.749
• Publications: 3 publications found

Genes affected

WDR59 (HGNC:25706): (WD repeat domain 59) Involved in cellular response to amino acid starvation and positive regulation of TOR signaling. Located in lysosomal membrane. Part of GATOR2 complex. [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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030581.4. 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
	WDR59	NM_030581.4	MANE Select	c.1713-2368G>T		intron	N/A	NP_085058.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR59	ENST00000262144.11	TSL:5 MANE Select	c.1713-2368G>T		intron	N/A	ENSP00000262144.6
	WDR59	ENST00000569229.5	TSL:5	c.360-2368G>T		intron	N/A	ENSP00000454382.1
	WDR59	ENST00000566924.1	TSL:4	n.107-2368G>T		intron	N/A	ENSP00000457978.1

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76307 AN: 151496 Hom.: 22059 Cov.: 29

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.503 AC: 76315 AN: 151614 Hom.: 22067 Cov.: 29 AF XY: 0.503 AC XY: 37275 AN XY: 74052

African (AFR) AF: 0.192 AC: 7955 AN: 41376

American (AMR) AF: 0.586 AC: 8915 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 2215 AN: 3466

East Asian (EAS) AF: 0.621 AC: 3195 AN: 5146

South Asian (SAS) AF: 0.545 AC: 2612 AN: 4792

European-Finnish (FIN) AF: 0.603 AC: 6320 AN: 10478

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.637 AC: 43190 AN: 67846

Other (OTH) AF: 0.529 AC: 1110 AN: 2100

Alfa AF: 0.598 Hom.: 104421

Bravo AF: 0.488

Asia WGS AF: 0.559 AC: 1940 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.54
DANN	Benign	0.49
PhyloP100		-0.75
Mutation Taster		=100/0	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: rs11149780; hg19: chr16-74940366;