Variant 16-74888208-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_030581.4(WDR59):c.2307T>C(p.Pro769Pro) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.925

Variant links:

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]

WDR59 links:

WDR59 (HGNC:):

WDR59 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
WDR59	NM_030581.4 linkuse as main transcript	c.2307T>C	p.Pro769Pro	synonymous_variant	22/26	ENST00000262144.11	NP_085058.3	Q6PJI9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
WDR59	ENST00000262144.11 linkuse as main transcript	c.2307T>C	p.Pro769Pro	synonymous_variant	22/26	5	NM_030581.4	ENSP00000262144.6	Q6PJI9-1
WDR59	ENST00000563797.5 linkuse as main transcript	c.289-453T>C		intron_variant		3		ENSP00000455060.1	H3BNY4
WDR59	ENST00000567018.5 linkuse as main transcript	n.*3T>C		downstream_gene_variant		3
WDR59	ENST00000569788.5 linkuse as main transcript	n.*36T>C		downstream_gene_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0200

AC:

3044

AN:

152036

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00482

AC XY:

654

AN XY:

135738

show subpopulations

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.:

AF XY:

0.00284

AC XY:

2062

AN XY:

727100

show subpopulations

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.:

Cov.:

AF XY:

0.0197

AC XY:

1464

AN XY:

74378

show subpopulations

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.:

Bravo

AF:

0.0224

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.000873

EpiControl

AF:

0.000711

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 21, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over