16-74888208-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_030581.4(WDR59):c.2307T>C(p.Pro769=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0046 in 1,613,718 control chromosomes in the GnomAD database, including 200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (89 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (111 hom.)
• Consequence: WDR59 NM_030581.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.925

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 16-74888208-A-G is Benign according to our data. Variant chr16-74888208-A-G is described in ClinVar as [Benign]. Clinvar id is 780187.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.925 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR59	NM_030581.4	c.2307T>C	p.Pro769=	synonymous_variant	22/26	ENST00000262144.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR59	ENST00000262144.11	c.2307T>C	p.Pro769=	synonymous_variant	22/26	5	NM_030581.4	P1
WDR59	ENST00000563797.5	c.291-453T>C		intron_variant		3
WDR59	ENST00000567018.5			downstream_gene_variant		3
WDR59	ENST00000569788.5			downstream_gene_variant		4

Frequencies

GnomAD3 genomes AF: 0.0200 AC: 3044 AN: 152036 Hom.: 89 Cov.: 32

Gnomad AFR AF: 0.0666

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00753

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000765

Gnomad OTH AF: 0.0187

GnomAD3 exomes AF: 0.00621 AC: 1560 AN: 251102 Hom.: 40 AF XY: 0.00482 AC XY: 654 AN XY: 135738

Gnomad AFR exome AF: 0.0669

Gnomad AMR exome AF: 0.00348

Gnomad ASJ exome AF: 0.0137

Gnomad EAS exome AF: 0.000709

Gnomad SAS exome AF: 0.00324

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000731

Gnomad OTH exome AF: 0.00326

GnomAD4 exome AF: 0.00299 AC: 4375 AN: 1461576 Hom.: 111 Cov.: 34 AF XY: 0.00284 AC XY: 2062 AN XY: 727100

Gnomad4 AFR exome AF: 0.0720

Gnomad4 AMR exome AF: 0.00430

Gnomad4 ASJ exome AF: 0.0142

Gnomad4 EAS exome AF: 0.000252

Gnomad4 SAS exome AF: 0.00348

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000559

Gnomad4 OTH exome AF: 0.00656

GnomAD4 genome AF: 0.0201 AC: 3051 AN: 152142 Hom.: 89 Cov.: 32 AF XY: 0.0197 AC XY: 1464 AN XY: 74378

Gnomad4 AFR AF: 0.0665

Gnomad4 AMR AF: 0.00746

Gnomad4 ASJ AF: 0.0179

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000765

Gnomad4 OTH AF: 0.0185

Alfa AF: 0.00661 Hom.: 36

Bravo AF: 0.0224

Asia WGS AF: 0.0110 AC: 39 AN: 3478

EpiCase AF: 0.000873

EpiControl AF: 0.000711

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 21, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	4.8
Dann	Benign	0.62

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: rs9940422; hg19: chr16-74922106;