19-12668379-G-C

Position:

• chr19-12668379-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016145.4(WDR83OS):​c.301C>G​(p.Pro101Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR83OS NM_016145.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.72

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR83OS	NM_016145.4	c.301C>G	p.Pro101Ala	missense_variant	4/4	ENST00000596731.7	NP_057229.1
WDR83	NM_001099737.3	c.-156-129G>C		intron_variant		ENST00000418543.8	NP_001093207.1
WDR83	NR_029375.2	n.187-129G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR83OS	ENST00000596731.7	c.301C>G	p.Pro101Ala	missense_variant	4/4	1	NM_016145.4	ENSP00000468969.1
WDR83	ENST00000418543.8	c.-156-129G>C		intron_variant		1	NM_001099737.3	ENSP00000402653.3
ENSG00000269590	ENST00000597961.1	c.150+749C>G		intron_variant		4		ENSP00000472710.1
ENSG00000285589	ENST00000648033.1	n.*4235C>G		non_coding_transcript_exon_variant	14/14			ENSP00000498000.1
ENSG00000285589	ENST00000648033.1	n.*4235C>G		3_prime_UTR_variant	14/14			ENSP00000498000.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 03, 2024

The c.301C>G (p.P101A) alteration is located in exon 4 (coding exon 4) of the WDR83OS gene. This alteration results from a C to G substitution at nucleotide position 301, causing the proline (P) at amino acid position 101 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.20	T;T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.68	D;D
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-5.1	.;D
REVEL	Uncertain	0.64
Sift	Benign	0.14	.;T
Sift4G	Benign	0.13	T;T
Polyphen		0.085	B;.
Vest4		0.76
MutPred		0.58		Loss of glycosylation at P101 (P = 0.0244);.;
MVP		0.25
MPC		0.67
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.56
gMVP		0.89

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: chr19-12779193;