19-12669365-G-C

Variant names:

• chr19-12669365-G-C
• rs62108388
• NM_016145.4:c.39C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016145.4(WDR83OS):​c.39C>G​(p.Asn13Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N13N) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: WDR83OS NM_016145.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.13
• 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]

ENSG00000269590 (HGNC:):

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2332007).

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.39C>G	p.Asn13Lys	missense	Exon 1 of 4	NP_057229.1	Q9Y284
	WDR83	NM_001099737.3	MANE Select	c.-36-390G>C		intron	N/A	NP_001093207.1	Q9BRX9
	WDR83	NR_029375.2		n.307-390G>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.39C>G	p.Asn13Lys	missense	Exon 1 of 4	ENSP00000468969.1	Q9Y284
	ENSG00000269590	ENST00000597961.1	TSL:4	c.33C>G	p.Asn11Lys	missense	Exon 1 of 5	ENSP00000472710.1	M0R2P5
	WDR83	ENST00000418543.8	TSL:1 MANE Select	c.-36-390G>C		intron	N/A	ENSP00000402653.3	Q9BRX9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451016 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 720880

African (AFR) AF: 0.00 AC: 0 AN: 33244

American (AMR) AF: 0.00 AC: 0 AN: 43160

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25860

East Asian (EAS) AF: 0.00 AC: 0 AN: 39298

South Asian (SAS) AF: 0.00 AC: 0 AN: 84708

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1106426

Other (OTH) AF: 0.00 AC: 0 AN: 59984

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.035	T
Eigen	Benign	0.072
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Benign	0.48	N
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.1
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.065
Sift	Benign	0.23	T
Sift4G	Benign	0.11	T
Polyphen		0.30	B
Vest4		0.45
MutPred		0.36		Gain of methylation at N13 (P = 0.003)
MVP		0.33
MPC		0.37
ClinPred		0.95	D
GERP RS		5.7
PromoterAI		0.0012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.61
gMVP		0.72
Mutation Taster		=58/42	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

dbSNP: rs62108388; hg19: chr19-12780179;