19-12669199-A-G

Position:

• chr19-12669199-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_016145.4(WDR83OS):​c.85T>C​(p.Leu29Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,614,090 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0060 (12 hom., cov: 32)
  • Exomes 𝑓: 0.00062 (12 hom.)
• Consequence: WDR83OS NM_016145.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.40

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 Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 19-12669199-A-G is Benign according to our data. Variant chr19-12669199-A-G is described in ClinVar as [Benign]. Clinvar id is 2044099.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.4 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00604 (919/152228) while in subpopulation AFR AF= 0.0211 (878/41520). AF 95% confidence interval is 0.02. There are 12 homozygotes in gnomad4. There are 446 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR83OS	NM_016145.4	c.85T>C	p.Leu29Leu	synonymous_variant	2/4	ENST00000596731.7	NP_057229.1
WDR83	NM_001099737.3	c.-36-556A>G		intron_variant		ENST00000418543.8	NP_001093207.1
WDR83	NR_029375.2	n.307-556A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR83OS	ENST00000596731.7	c.85T>C	p.Leu29Leu	synonymous_variant	2/4	1	NM_016145.4	ENSP00000468969.1
ENSG00000269590	ENST00000597961.1	c.79T>C	p.Leu27Leu	synonymous_variant	2/5	4		ENSP00000472710.1
WDR83	ENST00000418543.8	c.-36-556A>G		intron_variant		1	NM_001099737.3	ENSP00000402653.3
ENSG00000285589	ENST00000648033.1	n.*4019T>C		non_coding_transcript_exon_variant	12/14			ENSP00000498000.1
ENSG00000285589	ENST00000648033.1	n.*4019T>C		3_prime_UTR_variant	12/14			ENSP00000498000.1

Frequencies

GnomAD3 genomes AF: 0.00603 AC: 917 AN: 152110 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0212

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00182 AC: 457 AN: 251370 Hom.: 5 AF XY: 0.00134 AC XY: 182 AN XY: 135892

Gnomad AFR exome AF: 0.0240

Gnomad AMR exome AF: 0.00153

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000619 AC: 905 AN: 1461862 Hom.: 12 Cov.: 32 AF XY: 0.000572 AC XY: 416 AN XY: 727230

Gnomad4 AFR exome AF: 0.0211

Gnomad4 AMR exome AF: 0.00161

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000225

Gnomad4 OTH exome AF: 0.00142

GnomAD4 genome AF: 0.00604 AC: 919 AN: 152228 Hom.: 12 Cov.: 32 AF XY: 0.00599 AC XY: 446 AN XY: 74438

Gnomad4 AFR AF: 0.0211

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00218 Hom.: 2

Bravo AF: 0.00723

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 10, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	11
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs61748346; hg19: chr19-12780013;