chr6-33286888-A-G

Position:

• chr6-33286888-A-G

Variant summary

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

The NM_005452.6(WDR46):​c.1022T>C​(p.Val341Ala) variant causes a missense change. The variant allele was found at a frequency of 0.134 in 1,613,936 control chromosomes in the GnomAD database, including 15,849 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.10 (995 hom., cov: 31)
  • Exomes 𝑓: 0.14 (14854 hom.)
• Consequence: WDR46 NM_005452.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.17

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]

WDR46 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017456114).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR46	NM_005452.6	c.1022T>C	p.Val341Ala	missense_variant	10/15	ENST00000374617.9	NP_005443.3
WDR46	NM_001164267.2	c.860T>C	p.Val287Ala	missense_variant	10/15		NP_001157739.1
WDR46	XM_047419523.1	c.1022T>C	p.Val341Ala	missense_variant	10/14		XP_047275479.1
WDR46	XM_047419524.1	c.1022T>C	p.Val341Ala	missense_variant	10/11		XP_047275480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR46	ENST00000374617.9	c.1022T>C	p.Val341Ala	missense_variant	10/15	1	NM_005452.6	ENSP00000363746.4
WDR46	ENST00000444176.1	c.803T>C	p.Val268Ala	missense_variant	9/10	5		ENSP00000405568.1
WDR46	ENST00000489905.1	n.218T>C		non_coding_transcript_exon_variant	3/6	5

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15243 AN: 152132 Hom.: 990 Cov.: 31

Gnomad AFR AF: 0.0251

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.0723

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.0781

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.135

GnomAD3 exomes AF: 0.124 AC: 31139 AN: 250992 Hom.: 2297 AF XY: 0.132 AC XY: 17951 AN XY: 135680

Gnomad AFR exome AF: 0.0225

Gnomad AMR exome AF: 0.0772

Gnomad ASJ exome AF: 0.214

Gnomad EAS exome AF: 0.0634

Gnomad SAS exome AF: 0.202

Gnomad FIN exome AF: 0.0798

Gnomad NFE exome AF: 0.141

Gnomad OTH exome AF: 0.152

GnomAD4 exome AF: 0.137 AC: 200883 AN: 1461686 Hom.: 14854 Cov.: 35 AF XY: 0.140 AC XY: 101825 AN XY: 727170

Gnomad4 AFR exome AF: 0.0208

Gnomad4 AMR exome AF: 0.0812

Gnomad4 ASJ exome AF: 0.214

Gnomad4 EAS exome AF: 0.0622

Gnomad4 SAS exome AF: 0.203

Gnomad4 FIN exome AF: 0.0840

Gnomad4 NFE exome AF: 0.141

Gnomad4 OTH exome AF: 0.145

GnomAD4 genome AF: 0.100 AC: 15258 AN: 152250 Hom.: 995 Cov.: 31 AF XY: 0.0996 AC XY: 7411 AN XY: 74432

Gnomad4 AFR AF: 0.0250

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.0725

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.0781

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.139

Alfa AF: 0.135 Hom.: 3159

Bravo AF: 0.0979

TwinsUK AF: 0.152 AC: 565

ALSPAC AF: 0.144 AC: 555

ESP6500AA AF: 0.0295 AC: 130

ESP6500EA AF: 0.144 AC: 1237

ExAC AF: 0.125 AC: 15178

Asia WGS AF: 0.157 AC: 545 AN: 3478

EpiCase AF: 0.148

EpiControl AF: 0.146

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T;.
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.67	T;T
MetaRNN	Benign	0.0017	T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Pathogenic	3.4	M;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.9	D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.0040	D;.
Polyphen		1.0	D;.
Vest4		0.28
MPC		1.1
ClinPred		0.028	T
GERP RS		4.8
Varity_R		0.46
gMVP		0.74

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: rs14398; hg19: chr6-33254665;