rs11149780

chr16-74906468-C-Achr16-74906468-C-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR59	NM_030581.4	c.1713-2368G>T		intron_variant		ENST00000262144.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR59	ENST00000262144.11	c.1713-2368G>T		intron_variant		5	NM_030581.4	P1
WDR59	ENST00000569229.5	c.362-2368G>T		intron_variant		5
WDR59	ENST00000566924.1	c.107-2368G>T		intron_variant, NMD_transcript_variant		4
WDR59	ENST00000570070.1	n.306-2368G>T		intron_variant, non_coding_transcript_variant		4

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

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.586

Gnomad4 ASJ AF: 0.639

Gnomad4 EAS AF: 0.621

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.603

Gnomad4 NFE AF: 0.637

Gnomad4 OTH AF: 0.529

Alfa AF: 0.617 Hom.: 47125

Bravo AF: 0.488

Asia WGS AF: 0.559 AC: 1940 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.54
Dann	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs11149780; hg19: chr16-74940366;