16-74944720-G-A

Variant names:

• chr16-74944720-G-A
• rs2042415
• NM_030581.4:c.446-1894C>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.446-1894C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0705 in 151,996 control chromosomes in the GnomAD database, including 710 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 0.070 (710 hom., cov: 31)
• Consequence: WDR59 NM_030581.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.550
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.317 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.446-1894C>T		intron	N/A	NP_085058.3
	WDR59	NM_001324171.2		c.446-1894C>T		intron	N/A	NP_001311100.1
	WDR59	NM_001324172.2		c.446-1894C>T		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.446-1894C>T		intron	N/A	ENSP00000262144.6
	WDR59	ENST00000616369.4	TSL:1	c.446-1894C>T		intron	N/A	ENSP00000482446.1
	WDR59	ENST00000536050.5	TSL:2	c.383-1894C>T		intron	N/A	ENSP00000481730.1

Frequencies

GnomAD3 genomes AF: 0.0705 AC: 10711 AN: 151878 Hom.: 710 Cov.: 31

Gnomad AFR AF: 0.0166

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0392

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0620

Gnomad OTH AF: 0.0720

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

GnomAD4 genome AF: 0.0705 AC: 10714 AN: 151996 Hom.: 710 Cov.: 31 AF XY: 0.0772 AC XY: 5735 AN XY: 74280

African (AFR) AF: 0.0165 AC: 686 AN: 41508

American (AMR) AF: 0.122 AC: 1860 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.0392 AC: 136 AN: 3470

East Asian (EAS) AF: 0.330 AC: 1699 AN: 5142

South Asian (SAS) AF: 0.172 AC: 828 AN: 4802

European-Finnish (FIN) AF: 0.103 AC: 1083 AN: 10546

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

European-Non Finnish (NFE) AF: 0.0620 AC: 4212 AN: 67972

Other (OTH) AF: 0.0764 AC: 161 AN: 2106

Alfa AF: 0.0646 Hom.: 801

Bravo AF: 0.0689

Asia WGS AF: 0.234 AC: 813 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.36
DANN	Benign	0.57
PhyloP100		-0.55
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: rs2042415; hg19: chr16-74978618;