rs4888320

Positions:

• chr16-74957966-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030581.4(WDR59):​c.105-1356A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0915 in 152,084 control chromosomes in the GnomAD database, including 715 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 0.091 (715 hom., cov: 31)
• Consequence: WDR59 NM_030581.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.769

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR59	NM_030581.4	c.105-1356A>C		intron_variant		ENST00000262144.11	NP_085058.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR59	ENST00000262144.11	c.105-1356A>C		intron_variant		5	NM_030581.4	ENSP00000262144	P1

Frequencies

GnomAD3 genomes AF: 0.0915 AC: 13902 AN: 151966 Hom.: 714 Cov.: 31

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.0236

Gnomad EAS AF: 0.0401

Gnomad SAS AF: 0.0665

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0660

Gnomad OTH AF: 0.0908

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

GnomAD4 genome AF: 0.0915 AC: 13912 AN: 152084 Hom.: 715 Cov.: 31 AF XY: 0.0923 AC XY: 6861 AN XY: 74338

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.0236

Gnomad4 EAS AF: 0.0400

Gnomad4 SAS AF: 0.0657

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.0660

Gnomad4 OTH AF: 0.0922

Alfa AF: 0.0702 Hom.: 603

Bravo AF: 0.0964

Asia WGS AF: 0.0880 AC: 306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.6
DANN	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs4888320; hg19: chr16-74991864;