16-74956106-C-T

Variant names:

• chr16-74956106-C-T
• rs1943064
• NM_030581.4:c.240+369G>A

Variant summary

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

The NM_030581.4(WDR59):​c.240+369G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 151,918 control chromosomes in the GnomAD database, including 11,258 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 0.38 (11258 hom., cov: 31)
• Consequence: WDR59 NM_030581.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.702 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR59	NM_030581.4	MANE Select	c.240+369G>A		intron	N/A	NP_085058.3
	WDR59	NM_001324171.2		c.240+369G>A		intron	N/A	NP_001311100.1	Q6PJI9-2
	WDR59	NM_001324172.2		c.240+369G>A		intron	N/A	NP_001311101.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR59	ENST00000262144.11	TSL:5 MANE Select	c.240+369G>A		intron	N/A	ENSP00000262144.6	Q6PJI9-1
	WDR59	ENST00000616369.4	TSL:1	c.240+369G>A		intron	N/A	ENSP00000482446.1	Q6PJI9-2
	WDR59	ENST00000857980.1		c.384+225G>A		intron	N/A	ENSP00000528039.1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57081 AN: 151800 Hom.: 11248 Cov.: 31

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.376 AC: 57108 AN: 151918 Hom.: 11258 Cov.: 31 AF XY: 0.382 AC XY: 28349 AN XY: 74256

African (AFR) AF: 0.317 AC: 13150 AN: 41464

American (AMR) AF: 0.379 AC: 5795 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1122 AN: 3468

East Asian (EAS) AF: 0.721 AC: 3706 AN: 5140

South Asian (SAS) AF: 0.508 AC: 2439 AN: 4804

European-Finnish (FIN) AF: 0.411 AC: 4336 AN: 10556

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25394 AN: 67904

Other (OTH) AF: 0.353 AC: 744 AN: 2106

Alfa AF: 0.374 Hom.: 6159

Bravo AF: 0.370

Asia WGS AF: 0.560 AC: 1944 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.2
DANN	Benign	0.71
PhyloP100		-0.11
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: rs1943064; hg19: chr16-74990004;