16-74956106-C-T

Position:

• chr16-74956106-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR59	NM_030581.4	c.240+369G>A		intron_variant		ENST00000262144.11	NP_085058.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR59	ENST00000262144.11	c.240+369G>A		intron_variant		5	NM_030581.4	ENSP00000262144.6

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

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.721

Gnomad4 SAS AF: 0.508

Gnomad4 FIN AF: 0.411

Gnomad4 NFE AF: 0.374

Gnomad4 OTH AF: 0.353

Alfa AF: 0.364 Hom.: 2552

Bravo AF: 0.370

Asia WGS AF: 0.560 AC: 1944 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.2
DANN	Benign	0.71

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: rs1943064; hg19: chr16-74990004;