19-12669365-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_016145.4(WDR83OS):​c.39C>T​(p.Asn13Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0646 in 1,603,230 control chromosomes in the GnomAD database, including 4,119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.050 (326 hom., cov: 32)
  • Exomes 𝑓: 0.066 (3793 hom.)
• Consequence: WDR83OS NM_016145.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.13
• Publications: 6 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: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 19-12669365-G-A is Benign according to our data. Variant chr19-12669365-G-A is described in ClinVar as Benign. ClinVar VariationId is 2039025.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.13 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.07 is higher than 0.05.

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>T	p.Asn13Asn	synonymous	Exon 1 of 4	NP_057229.1	Q9Y284
	WDR83	NM_001099737.3	MANE Select	c.-36-390G>A		intron	N/A	NP_001093207.1	Q9BRX9
	WDR83	NR_029375.2		n.307-390G>A		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>T	p.Asn13Asn	synonymous	Exon 1 of 4	ENSP00000468969.1	Q9Y284
	ENSG00000269590	ENST00000597961.1	TSL:4	c.33C>T	p.Asn11Asn	synonymous	Exon 1 of 5	ENSP00000472710.1	M0R2P5
	WDR83	ENST00000418543.8	TSL:1 MANE Select	c.-36-390G>A		intron	N/A	ENSP00000402653.3	Q9BRX9

Frequencies

GnomAD3 genomes AF: 0.0499 AC: 7588 AN: 152172 Hom.: 326 Cov.: 32

Gnomad AFR AF: 0.0151

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0246

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00995

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0717

Gnomad OTH AF: 0.0350

GnomAD2 exomes AF: 0.0507 AC: 11697 AN: 230570 AF XY: 0.0501

Gnomad AFR exome AF: 0.0147

Gnomad AMR exome AF: 0.0179

Gnomad ASJ exome AF: 0.0142

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.143

Gnomad NFE exome AF: 0.0713

Gnomad OTH exome AF: 0.0529

GnomAD4 exome AF: 0.0662 AC: 95997 AN: 1450940 Hom.: 3793 Cov.: 32 AF XY: 0.0643 AC XY: 46364 AN XY: 720848

African (AFR) AF: 0.0116 AC: 385 AN: 33244

American (AMR) AF: 0.0188 AC: 813 AN: 43156

Ashkenazi Jewish (ASJ) AF: 0.0142 AC: 368 AN: 25860

East Asian (EAS) AF: 0.000102 AC: 4 AN: 39298

South Asian (SAS) AF: 0.0119 AC: 1012 AN: 84704

European-Finnish (FIN) AF: 0.138 AC: 7278 AN: 52562

Middle Eastern (MID) AF: 0.00504 AC: 29 AN: 5758

European-Non Finnish (NFE) AF: 0.0748 AC: 82718 AN: 1106378

Other (OTH) AF: 0.0565 AC: 3390 AN: 59980

GnomAD4 genome AF: 0.0498 AC: 7588 AN: 152290 Hom.: 326 Cov.: 32 AF XY: 0.0509 AC XY: 3789 AN XY: 74474

African (AFR) AF: 0.0150 AC: 624 AN: 41564

American (AMR) AF: 0.0246 AC: 376 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0150 AC: 52 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.0102 AC: 49 AN: 4822

European-Finnish (FIN) AF: 0.140 AC: 1482 AN: 10598

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0717 AC: 4878 AN: 68024

Other (OTH) AF: 0.0346 AC: 73 AN: 2110

Alfa AF: 0.0507 Hom.: 274

Bravo AF: 0.0405

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	12
DANN	Benign	0.94
PhyloP100		2.1
PromoterAI		-0.091	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=98/2	polymorphism (auto)

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;