rs463260

Positions:

• chr6-33289207-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005452.6(WDR46):​c.-37G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 1,592,550 control chromosomes in the GnomAD database, including 235,887 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 0.59 (27320 hom., cov: 30)
  • Exomes 𝑓: 0.53 (208567 hom.)
• Consequence: WDR46 NM_005452.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

Genes affected

WDR46 (HGNC:13923): (WD repeat domain 46) Enables RNA binding activity. Predicted to be involved in maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). Predicted to be located in nucleoplasm. Predicted to be part of small-subunit processome. Predicted to be active in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

PFDN6 (HGNC:4926): (prefoldin subunit 6) PFDN6 is a subunit of the heteromeric prefoldin complex that chaperones nascent actin (see MIM 102560) and alpha- and beta-tubulin (see MIM 602529 and MIM 191130, respectively) chains pending their transfer to the cytosolic chaperonin containing TCP1 (MIM 186980) (CCT) complex (Hansen et al., 1999 [PubMed 10209023]).[supplied by OMIM, Jul 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR46	NM_005452.6	c.-37G>A		5_prime_UTR_variant	1/15	ENST00000374617.9	NP_005443.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR46	ENST00000374617.9	c.-37G>A		5_prime_UTR_variant	1/15	1	NM_005452.6	ENSP00000363746.4
WDR46	ENST00000477718.5	n.41G>A		non_coding_transcript_exon_variant	1/7	5
WDR46	ENST00000468157.5	n.-5G>A		upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89798 AN: 151752 Hom.: 27267 Cov.: 30

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.590

GnomAD3 exomes AF: 0.555 AC: 131499 AN: 236830 Hom.: 37333 AF XY: 0.557 AC XY: 71774 AN XY: 128748

Gnomad AFR exome AF: 0.750

Gnomad AMR exome AF: 0.534

Gnomad ASJ exome AF: 0.596

Gnomad EAS exome AF: 0.368

Gnomad SAS exome AF: 0.627

Gnomad FIN exome AF: 0.528

Gnomad NFE exome AF: 0.545

Gnomad OTH exome AF: 0.568

GnomAD4 exome AF: 0.535 AC: 770446 AN: 1440680 Hom.: 208567 Cov.: 72 AF XY: 0.538 AC XY: 384998 AN XY: 715540

Gnomad4 AFR exome AF: 0.747

Gnomad4 AMR exome AF: 0.537

Gnomad4 ASJ exome AF: 0.598

Gnomad4 EAS exome AF: 0.349

Gnomad4 SAS exome AF: 0.625

Gnomad4 FIN exome AF: 0.528

Gnomad4 NFE exome AF: 0.526

Gnomad4 OTH exome AF: 0.557

GnomAD4 genome AF: 0.592 AC: 89904 AN: 151870 Hom.: 27320 Cov.: 30 AF XY: 0.592 AC XY: 43922 AN XY: 74182

Gnomad4 AFR AF: 0.736

Gnomad4 AMR AF: 0.579

Gnomad4 ASJ AF: 0.608

Gnomad4 EAS AF: 0.391

Gnomad4 SAS AF: 0.624

Gnomad4 FIN AF: 0.527

Gnomad4 NFE AF: 0.532

Gnomad4 OTH AF: 0.588

Alfa AF: 0.552 Hom.: 14912

Bravo AF: 0.600

Asia WGS AF: 0.513 AC: 1787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.3
DANN	Benign	0.84

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: rs463260; hg19: chr6-33256984;