rs4888320

Variant names:

• chr16-74957966-T-G
• rs4888320
• NM_030581.4:c.105-1356A>C

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.134 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.105-1356A>C		intron	N/A	NP_085058.3
	WDR59	NM_001324171.2		c.105-1356A>C		intron	N/A	NP_001311100.1
	WDR59	NM_001324172.2		c.105-1356A>C		intron	N/A	NP_001311101.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR59	ENST00000262144.11	TSL:5 MANE Select	c.105-1356A>C		intron	N/A	ENSP00000262144.6
	WDR59	ENST00000616369.4	TSL:1	c.105-1356A>C		intron	N/A	ENSP00000482446.1
	WDR59	ENST00000536050.5	TSL:2	c.42-1356A>C		intron	N/A	ENSP00000481730.1

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

African (AFR) AF: 0.128 AC: 5306 AN: 41486

American (AMR) AF: 0.139 AC: 2119 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0236 AC: 82 AN: 3472

East Asian (EAS) AF: 0.0400 AC: 207 AN: 5174

South Asian (SAS) AF: 0.0657 AC: 317 AN: 4822

European-Finnish (FIN) AF: 0.110 AC: 1163 AN: 10562

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0660 AC: 4489 AN: 67978

Other (OTH) AF: 0.0922 AC: 195 AN: 2114

Alfa AF: 0.0710 Hom.: 745

Bravo AF: 0.0964

Asia WGS AF: 0.0880 AC: 306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.6
DANN	Benign	0.60
PhyloP100		-0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs4888320; hg19: chr16-74991864;