NM_016145.4:c.298C>G

Variant names:

• chr19-12668382-G-C
• rs773514362
• NM_016145.4:c.298C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016145.4(WDR83OS):​c.298C>G​(p.Gln100Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,132 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: WDR83OS NM_016145.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.72
• Publications: 0 publications found

Genes affected

WDR83OS (HGNC:30203): (WD repeat domain 83 opposite strand) Enables protein folding chaperone. Involved in protein insertion into ER membrane. Is integral component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

WDR83 (HGNC:32672): (WD repeat domain 83) This gene encodes a member of the WD-40 protein family. The protein is proposed to function as a molecular scaffold for various multimeric protein complexes. The protein associates with several components of the extracellular signal-regulated kinase (ERK) pathway, and promotes ERK activity in response to serum or other signals. The protein also interacts with egl nine homolog 3 (EGLN3, also known as PHD3) and regulates expression of hypoxia-inducible factor 1, and has been purified as part of the spliceosome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

ENSG00000269590 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016145.4. 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
	WDR83OS	NM_016145.4	MANE Select	c.298C>G	p.Gln100Glu	missense	Exon 4 of 4	NP_057229.1	Q9Y284
	WDR83	NM_001099737.3	MANE Select	c.-156-126G>C		intron	N/A	NP_001093207.1	Q9BRX9
	WDR83	NR_029375.2		n.187-126G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR83OS	ENST00000596731.7	TSL:1 MANE Select	c.298C>G	p.Gln100Glu	missense	Exon 4 of 4	ENSP00000468969.1	Q9Y284
	WDR83	ENST00000418543.8	TSL:1 MANE Select	c.-156-126G>C		intron	N/A	ENSP00000402653.3	Q9BRX9
	ENSG00000269590	ENST00000597961.1	TSL:4	c.150+746C>G		intron	N/A	ENSP00000472710.1	M0R2P5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461132 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726758

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86024

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111752

Other (OTH) AF: 0.00 AC: 0 AN: 60366

GnomAD4 genome Cov.: 32

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	0.32
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.098	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		8.7
PrimateAI	Uncertain	0.67	T
REVEL	Benign	0.18
Sift4G	Benign	0.30	T
Polyphen		0.38	B
Vest4		0.72
MutPred		0.30		Gain of glycosylation at P99 (P = 0.0672)
MVP		0.072
MPC		0.53
ClinPred		0.96	D
GERP RS		5.7
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1
Varity_R		0.80
gMVP		0.92
Mutation Taster		=42/58	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs773514362; hg19: chr19-12779196;