11-62834479-T-C

Position:

• chr11-62834479-T-C

Variant summary

Our verdict is Likely benign. Variant got -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. 15/21 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

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]

ACMG classification

Verdict is Likely_benign. Variant got -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 id is 2325890.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR74	NM_001369450.1	c.667A>G	p.Thr223Ala	missense_variant	7/11	ENST00000278856.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR74	ENST00000278856.9	c.667A>G	p.Thr223Ala	missense_variant	7/11	1	NM_001369450.1	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 10, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

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
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.55	T;T;.;.;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.049	T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.52	N;N;N;N;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.13	N;N;N;N;N
REVEL	Benign	0.019
Sift	Benign	0.56	T;T;T;T;T
Sift4G	Benign	0.43	T;T;T;T;T
Polyphen		0.0	B;B;B;B;B
Vest4		0.21
MutPred		0.24		Loss of glycosylation at T223 (P = 0.0339);Loss of glycosylation at T223 (P = 0.0339);Loss of glycosylation at T223 (P = 0.0339);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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-62601951;