rs117131055

Variant names:

• chr19-12669390-T-A
• rs117131055
• NM_016145.4:c.14A>T

Your query was ambiguous. Multiple possible variants found:

• chr19-12669390-T-A
• chr19-12669390-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016145.4(WDR83OS):​c.14A>T​(p.Asn5Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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: Not reported in ClinVar
• Conservation: PhyloP100: -0.615

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08150023).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR83OS	NM_016145.4	c.14A>T	p.Asn5Ile	missense_variant	Exon 1 of 4	ENST00000596731.7	NP_057229.1
WDR83	NM_001099737.3	c.-36-365T>A		intron_variant	Intron 2 of 10	ENST00000418543.8	NP_001093207.1
WDR83	NR_029375.2	n.307-365T>A		intron_variant	Intron 2 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR83OS	ENST00000596731.7	c.14A>T	p.Asn5Ile	missense_variant	Exon 1 of 4	1	NM_016145.4	ENSP00000468969.1
ENSG00000269590	ENST00000597961.1	c.8A>T	p.Asn3Ile	missense_variant	Exon 1 of 5	4		ENSP00000472710.1
WDR83	ENST00000418543.8	c.-36-365T>A		intron_variant	Intron 2 of 10	1	NM_001099737.3	ENSP00000402653.3
ENSG00000285589	ENST00000648033.1	n.*3948A>T		non_coding_transcript_exon_variant	Exon 11 of 14			ENSP00000498000.1
ENSG00000285589	ENST00000648033.1	n.*3948A>T		3_prime_UTR_variant	Exon 11 of 14			ENSP00000498000.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	1.5
DANN	Benign	0.95
DEOGEN2	Benign	0.038	.;T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.76	T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.082	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	.;L;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.9	.;.;N
REVEL	Benign	0.027
Sift	Uncertain	0.0020	.;.;D
Sift4G	Uncertain	0.0050	D;D;D
Polyphen		0.27	.;B;.
Vest4		0.35, 0.47
MutPred		0.36		.;Gain of catalytic residue at N5 (P = 0.0035);Gain of catalytic residue at N5 (P = 0.0035);
MVP		0.39
MPC		0.68
ClinPred		0.37	T
GERP RS		-2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.37
gMVP		0.69

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

LitVar

Other links and lift over

dbSNP: rs117131055; hg19: chr19-12780204;