19-12668380-CTG-TTC

Variant names:

• chr19-12668380-CTG-TTC
• NM_016145.4:c.298_300delCAGinsGAA
• WDR83OS p.Gln100Glu

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_016145.4(WDR83OS):​c.298_300delCAGinsGAA​(p.Gln100Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR83OS NM_016145.4 missense
• Clinical Significance: Not reported in ClinVar
• 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 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.298_300delCAGinsGAA	p.Gln100Glu	missense	N/A	NP_057229.1	Q9Y284
	WDR83	NM_001099737.3	MANE Select	c.-156-128_-156-126delCTGinsTTC		intron	N/A	NP_001093207.1	Q9BRX9
	WDR83	NR_029375.2		n.187-128_187-126delCTGinsTTC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR83OS	ENST00000596731.7	TSL:1 MANE Select	c.298_300delCAGinsGAA	p.Gln100Glu	missense	N/A	ENSP00000468969.1	Q9Y284
	WDR83	ENST00000418543.8	TSL:1 MANE Select	c.-156-128_-156-126delCTGinsTTC		intron	N/A	ENSP00000402653.3	Q9BRX9
	ENSG00000269590	ENST00000597961.1	TSL:4	c.150+746_150+748delCAGinsGAA		intron	N/A	ENSP00000472710.1	M0R2P5

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-12779194;