rs34069323

Variant names:

• chr15-84644014-T-C
• rs34069323
• ENST00000348993.10:n.5522T>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000348993.10(ENSG00000291159):​n.5522T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00738 in 319,500 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0062 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0085 (14 hom.)
• Consequence: ENSG00000291159 ENST00000348993.10 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81
• Publications: 3 publications found

Genes affected

ENSG00000291159 (HGNC:58684):

WDR73 (HGNC:25928): (WD repeat domain 73) The protein encoded by this gene is thought to contain multiple WD40 repeats. WD40 repeats are motifs that contain 40-60 amino acids, and usually end with Trp-Asp (WD). This protein is found in the cytoplasm during interphase, but accumulates at the spindle poles and astral microtubules during mitosis. Reduced expression of this gene results in abnormalities in the size and morphology of the nucleus. Mutations in this gene have been associated with Galloway-Mowat syndrome PMID: 25466283), which is a rare autosomal recessive disorder that affects both the central nervous system and kidneys. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

WDR73 Gene-Disease associations (from GenCC):

• Galloway-Mowat syndrome 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• CAMOS syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Galloway-Mowat syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS2: High Homozygotes in GnomAd4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000348993.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR73	NM_032856.5	MANE Select	c.884-291A>G		intron	N/A	NP_116245.2
	WDR73	NR_130944.2		n.1427-291A>G		intron	N/A
	WDR73	NR_130945.2		n.1006-291A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000291159	ENST00000348993.10	TSL:1	n.5522T>C		non_coding_transcript_exon	Exon 4 of 4
	WDR73	ENST00000434634.7	TSL:1 MANE Select	c.884-291A>G		intron	N/A	ENSP00000387982.3
	WDR73	ENST00000398528.7	TSL:1	n.960-291A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00619 AC: 942 AN: 152200 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00229

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00563

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0114

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00971

Gnomad OTH AF: 0.00813

GnomAD4 exome AF: 0.00846 AC: 1415 AN: 167182 Hom.: 14 Cov.: 0 AF XY: 0.00877 AC XY: 788 AN XY: 89888

African (AFR) AF: 0.000905 AC: 4 AN: 4420

American (AMR) AF: 0.00496 AC: 28 AN: 5644

Ashkenazi Jewish (ASJ) AF: 0.00470 AC: 23 AN: 4892

East Asian (EAS) AF: 0.00 AC: 0 AN: 8108

South Asian (SAS) AF: 0.0137 AC: 337 AN: 24546

European-Finnish (FIN) AF: 0.00165 AC: 12 AN: 7290

Middle Eastern (MID) AF: 0.0122 AC: 8 AN: 658

European-Non Finnish (NFE) AF: 0.00917 AC: 941 AN: 102568

Other (OTH) AF: 0.00685 AC: 62 AN: 9056

GnomAD4 genome AF: 0.00619 AC: 943 AN: 152318 Hom.: 4 Cov.: 32 AF XY: 0.00518 AC XY: 386 AN XY: 74488

African (AFR) AF: 0.00229 AC: 95 AN: 41558

American (AMR) AF: 0.00562 AC: 86 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00404 AC: 14 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.0114 AC: 55 AN: 4822

European-Finnish (FIN) AF: 0.00113 AC: 12 AN: 10626

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00972 AC: 661 AN: 68034

Other (OTH) AF: 0.00804 AC: 17 AN: 2114

Alfa AF: 0.00818 Hom.: 0

Bravo AF: 0.00665

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.55
DANN	Benign	0.64
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs34069323; hg19: chr15-85187245;