chr11-62834436-G-T

Variant names:

• chr11-62834436-G-T
• rs767241559
• NM_001369450.1:c.710C>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001369450.1(WDR74):​c.710C>A​(p.Pro237Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000351 in 1,139,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P237L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: WDR74 NM_001369450.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.00
• Publications: 0 publications found

Genes affected

WDR74 (HGNC:25529): (WD repeat domain 74) Involved in rRNA processing and ribosomal large subunit biogenesis. Located in nucleoplasm. Colocalizes with nuclear exosome (RNase complex) and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

STX5-DT (HGNC:55488): (STX5 divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.746

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369450.1. 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
	WDR74	NM_001369450.1	MANE Select	c.710C>A	p.Pro237Gln	missense	Exon 7 of 11	NP_001356379.1	Q6RFH5-1
	WDR74	NM_001369447.1		c.752C>A	p.Pro251Gln	missense	Exon 7 of 11	NP_001356376.1
	WDR74	NM_001369451.1		c.710C>A	p.Pro237Gln	missense	Exon 8 of 12	NP_001356380.1	Q6RFH5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR74	ENST00000278856.9	TSL:1 MANE Select	c.710C>A	p.Pro237Gln	missense	Exon 7 of 11	ENSP00000278856.4	Q6RFH5-1
	WDR74	ENST00000311713.11	TSL:1	c.710C>A	p.Pro237Gln	missense	Exon 7 of 10	ENSP00000308931.7	Q6RFH5-2
	WDR74	ENST00000892916.1		c.752C>A	p.Pro251Gln	missense	Exon 8 of 12	ENSP00000562975.1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD2 exomes AF: 0.00000404 AC: 1 AN: 247290 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000351 AC: 4 AN: 1139822 Hom.: 0 Cov.: 39 AF XY: 0.00000352 AC XY: 2 AN XY: 567902

African (AFR) AF: 0.00 AC: 0 AN: 24878

American (AMR) AF: 0.00 AC: 0 AN: 37534

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16748

East Asian (EAS) AF: 0.00 AC: 0 AN: 17424

South Asian (SAS) AF: 0.0000365 AC: 3 AN: 82168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34240

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4294

European-Non Finnish (NFE) AF: 0.00000114 AC: 1 AN: 880794

Other (OTH) AF: 0.00 AC: 0 AN: 41742

GnomAD4 genome Cov.: 26

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.016	T
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		5.0
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.21
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.031	D
Polyphen		0.99	D
Vest4		0.70
MutPred		0.49		Loss of glycosylation at T234 (P = 0.0424)
MVP		0.65
MPC		0.42
ClinPred		0.91	D
GERP RS		4.3
Varity_R		0.19
gMVP		0.54
Mutation Taster		=76/24	polymorphism

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: rs767241559; hg19: chr11-62601908;