NM_001369450.1:c.710C>T

Variant names:

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

Variant summary

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

The NM_001369450.1(WDR74):​c.710C>T​(p.Pro237Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000316 in 1,234,998 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P237R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000032 (0 hom., cov: 26)
  • Exomes 𝑓: 0.000032 (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 0 ACMG points.

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>T	p.Pro237Leu	missense	Exon 7 of 11	NP_001356379.1	Q6RFH5-1
	WDR74	NM_001369447.1		c.752C>T	p.Pro251Leu	missense	Exon 7 of 11	NP_001356376.1
	WDR74	NM_001369451.1		c.710C>T	p.Pro237Leu	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>T	p.Pro237Leu	missense	Exon 7 of 11	ENSP00000278856.4	Q6RFH5-1
	WDR74	ENST00000311713.11	TSL:1	c.710C>T	p.Pro237Leu	missense	Exon 7 of 10	ENSP00000308931.7	Q6RFH5-2
	WDR74	ENST00000892916.1		c.752C>T	p.Pro251Leu	missense	Exon 8 of 12	ENSP00000562975.1

Frequencies

GnomAD3 genomes AF: 0.0000315 AC: 3 AN: 95176 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.0000418

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000765

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000526 AC: 13 AN: 247290 AF XY: 0.0000447

Gnomad AFR exome AF: 0.0000655

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000179

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000316 AC: 36 AN: 1139822 Hom.: 0 Cov.: 39 AF XY: 0.0000317 AC XY: 18 AN XY: 567902

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

American (AMR) AF: 0.0000266 AC: 1 AN: 37534

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

East Asian (EAS) AF: 0.0000574 AC: 1 AN: 17424

South Asian (SAS) AF: 0.000256 AC: 21 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: 0.00000908 AC: 8 AN: 880794

Other (OTH) AF: 0.000120 AC: 5 AN: 41742

GnomAD4 genome AF: 0.0000315 AC: 3 AN: 95176 Hom.: 0 Cov.: 26 AF XY: 0.0000465 AC XY: 2 AN XY: 42996

African (AFR) AF: 0.0000418 AC: 1 AN: 23952

American (AMR) AF: 0.00 AC: 0 AN: 5980

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2844

East Asian (EAS) AF: 0.00 AC: 0 AN: 2742

South Asian (SAS) AF: 0.000765 AC: 2 AN: 2614

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 70

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52636

Other (OTH) AF: 0.00 AC: 0 AN: 1214

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000579 AC: 7

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	0.093
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.30
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		5.0
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Benign	0.18
Sift	Uncertain	0.013	D
Sift4G	Benign	0.091	T
Polyphen		0.98	D
Vest4		0.57
MVP		0.58
MPC		0.41
ClinPred		0.29	T
GERP RS		4.3
Varity_R		0.19
gMVP		0.61
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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;