6-33289207-C-T

Variant names:

• chr6-33289207-C-T
• rs463260
• NM_005452.6:c.-37G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 23 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005452.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR46	NM_005452.6	MANE Select	c.-37G>A		5_prime_UTR	Exon 1 of 15	NP_005443.3
	WDR46	NM_001164267.2		c.-37G>A		5_prime_UTR	Exon 1 of 15	NP_001157739.1	A0A1U9X8W1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR46	ENST00000374617.9	TSL:1 MANE Select	c.-37G>A		5_prime_UTR	Exon 1 of 15	ENSP00000363746.4	O15213
	PFDN6	ENST00000883725.1		c.-161C>T		5_prime_UTR	Exon 1 of 5	ENSP00000553784.1
	PFDN6	ENST00000940443.1		c.-161C>T		5_prime_UTR	Exon 2 of 6	ENSP00000610502.1

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

GnomAD2 exomes AF: 0.555 AC: 131499 AN: 236830 AF XY: 0.557

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 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

African (AFR) AF: 0.747 AC: 24332 AN: 32566

American (AMR) AF: 0.537 AC: 21855 AN: 40704

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 15034 AN: 25120

East Asian (EAS) AF: 0.349 AC: 13770 AN: 39442

South Asian (SAS) AF: 0.625 AC: 52805 AN: 84450

European-Finnish (FIN) AF: 0.528 AC: 26999 AN: 51120

Middle Eastern (MID) AF: 0.578 AC: 3192 AN: 5524

European-Non Finnish (NFE) AF: 0.526 AC: 579334 AN: 1102300

Other (OTH) AF: 0.557 AC: 33125 AN: 59454

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

African (AFR) AF: 0.736 AC: 30474 AN: 41404

American (AMR) AF: 0.579 AC: 8846 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2105 AN: 3464

East Asian (EAS) AF: 0.391 AC: 2017 AN: 5162

South Asian (SAS) AF: 0.624 AC: 3002 AN: 4812

European-Finnish (FIN) AF: 0.527 AC: 5535 AN: 10498

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.532 AC: 36165 AN: 67934

Other (OTH) AF: 0.588 AC: 1242 AN: 2112

Alfa AF: 0.575 Hom.: 37276

Bravo AF: 0.600

Asia WGS AF: 0.513 AC: 1787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.3
DANN	Benign	0.84
PhyloP100		-1.2
PromoterAI		-0.020	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs463260; hg19: chr6-33256984; COSMIC: COSV108226778; COSMIC: COSV108226778;