chr19-12669382-C-A

Variant names:

• chr19-12669382-C-A
• NM_016145.4:c.22G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_016145.4(WDR83OS):​c.22G>T​(p.Asp8Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000207 in 1,449,000 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: WDR83OS NM_016145.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.62

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.749

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR83OS	NM_016145.4	c.22G>T	p.Asp8Tyr	missense_variant	Exon 1 of 4	ENST00000596731.7	NP_057229.1
WDR83	NM_001099737.3	c.-36-373C>A		intron_variant	Intron 2 of 10	ENST00000418543.8	NP_001093207.1
WDR83	NR_029375.2	n.307-373C>A		intron_variant	Intron 2 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR83OS	ENST00000596731.7	c.22G>T	p.Asp8Tyr	missense_variant	Exon 1 of 4	1	NM_016145.4	ENSP00000468969.1
ENSG00000269590	ENST00000597961.1	c.16G>T	p.Asp6Tyr	missense_variant	Exon 1 of 5	4		ENSP00000472710.1
WDR83	ENST00000418543.8	c.-36-373C>A		intron_variant	Intron 2 of 10	1	NM_001099737.3	ENSP00000402653.3
ENSG00000285589	ENST00000648033.1	n.*3956G>T		non_coding_transcript_exon_variant	Exon 11 of 14			ENSP00000498000.1
ENSG00000285589	ENST00000648033.1	n.*3956G>T		3_prime_UTR_variant	Exon 11 of 14			ENSP00000498000.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1449000 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 719640

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000271

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	.;T;T
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.076	D
MetaRNN	Pathogenic	0.75	D;D;D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Pathogenic	3.0	.;M;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-5.7	.;.;D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0020	.;.;D
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		1.0	.;D;.
Vest4		0.91, 0.93
MutPred		0.59		.;Gain of MoRF binding (P = 0.034);Gain of MoRF binding (P = 0.034);
MVP		0.74
MPC		1.1
ClinPred		1.0	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.93
gMVP		0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr19-12780196;