16-74874248-G-A

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.2886C>T(p.Thr962=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00415 in 1,614,102 control chromosomes in the GnomAD database, including 163 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (60 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (103 hom.)
• Consequence: WDR59 NM_030581.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.59

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 16-74874248-G-A is Benign according to our data. Variant chr16-74874248-G-A is described in ClinVar as [Benign]. Clinvar id is 780186.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.59 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR59	NM_030581.4	c.2886C>T	p.Thr962=	synonymous_variant	26/26	ENST00000262144.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR59	ENST00000262144.11	c.2886C>T	p.Thr962=	synonymous_variant	26/26	5	NM_030581.4	P1
WDR59	ENST00000569183.1	n.780C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.0171 AC: 2599 AN: 152180 Hom.: 59 Cov.: 32

Gnomad AFR AF: 0.0561

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00694

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.000773

Gnomad SAS AF: 0.00621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000794

Gnomad OTH AF: 0.0153

GnomAD3 exomes AF: 0.00576 AC: 1447 AN: 251132 Hom.: 38 AF XY: 0.00458 AC XY: 622 AN XY: 135780

Gnomad AFR exome AF: 0.0558

Gnomad AMR exome AF: 0.00327

Gnomad ASJ exome AF: 0.00933

Gnomad EAS exome AF: 0.000817

Gnomad SAS exome AF: 0.00670

Gnomad FIN exome AF: 0.0000925

Gnomad NFE exome AF: 0.000784

Gnomad OTH exome AF: 0.00392

GnomAD4 exome AF: 0.00279 AC: 4079 AN: 1461804 Hom.: 103 Cov.: 31 AF XY: 0.00275 AC XY: 2000 AN XY: 727204

Gnomad4 AFR exome AF: 0.0596

Gnomad4 AMR exome AF: 0.00429

Gnomad4 ASJ exome AF: 0.00968

Gnomad4 EAS exome AF: 0.000403

Gnomad4 SAS exome AF: 0.00627

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.000539

Gnomad4 OTH exome AF: 0.00654

GnomAD4 genome AF: 0.0172 AC: 2623 AN: 152298 Hom.: 60 Cov.: 32 AF XY: 0.0166 AC XY: 1235 AN XY: 74462

Gnomad4 AFR AF: 0.0563

Gnomad4 AMR AF: 0.00686

Gnomad4 ASJ AF: 0.0124

Gnomad4 EAS AF: 0.000969

Gnomad4 SAS AF: 0.00621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000794

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.00737 Hom.: 17

Bravo AF: 0.0193

Asia WGS AF: 0.0280 AC: 98 AN: 3478

EpiCase AF: 0.000981

EpiControl AF: 0.00101

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	0.25
Dann	Benign	0.52

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: rs61733724; hg19: chr16-74908146;