11-62834479-T-C

Variant names:

• chr11-62834479-T-C
• NM_001369450.1:c.667A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001369450.1(WDR74):​c.667A>G​(p.Thr223Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: WDR74 NM_001369450.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.125
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048517227).
• BP6: Variant 11-62834479-T-C is Benign according to our data. Variant chr11-62834479-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2325890.Status of the report is criteria_provided_single_submitter, 1 stars.

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.667A>G	p.Thr223Ala	missense	Exon 7 of 11	NP_001356379.1	Q6RFH5-1
	WDR74	NM_001369447.1		c.709A>G	p.Thr237Ala	missense	Exon 7 of 11	NP_001356376.1
	WDR74	NM_001369451.1		c.667A>G	p.Thr223Ala	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.667A>G	p.Thr223Ala	missense	Exon 7 of 11	ENSP00000278856.4	Q6RFH5-1
	WDR74	ENST00000311713.11	TSL:1	c.667A>G	p.Thr223Ala	missense	Exon 7 of 10	ENSP00000308931.7	Q6RFH5-2
	WDR74	ENST00000892916.1		c.709A>G	p.Thr237Ala	missense	Exon 8 of 12	ENSP00000562975.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.053
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	14
DANN	Benign	0.87
DEOGEN2	Benign	0.0062	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.52	N
PhyloP100		0.13
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.019
Sift	Benign	0.56	T
Sift4G	Benign	0.43	T
Polyphen		0.0	B
Vest4		0.21
MutPred		0.24		Loss of glycosylation at T223 (P = 0.0339)
MVP		0.11
MPC		0.34
ClinPred		0.027	T
GERP RS		-0.28
Varity_R		0.024
gMVP		0.25
Mutation Taster		=98/2	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

hg19: chr11-62601951;