15-84643346-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032856.5(WDR73):c.*124G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 1,218,342 control chromosomes in the GnomAD database, including 35,480 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3563 hom., cov: 32)
  • Exomes 𝑓: 0.24 (31917 hom.)
• Consequence: WDR73 NM_032856.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.68

Genes affected

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 15-84643346-C-T is Benign according to our data. Variant chr15-84643346-C-T is described in ClinVar as [Benign]. Clinvar id is 1226394.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR73	NM_032856.5	c.*124G>A		3_prime_UTR_variant	8/8	ENST00000434634.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR73	ENST00000434634.7	c.*124G>A		3_prime_UTR_variant	8/8	1	NM_032856.5	P1
	ENST00000348993.9	n.4843C>T		non_coding_transcript_exon_variant	4/4	1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31119 AN: 152028 Hom.: 3562 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.214

GnomAD4 exome AF: 0.239 AC: 255090 AN: 1066196 Hom.: 31917 Cov.: 14 AF XY: 0.239 AC XY: 125603 AN XY: 526590

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.185

Gnomad4 ASJ exome AF: 0.258

Gnomad4 EAS exome AF: 0.0974

Gnomad4 SAS exome AF: 0.166

Gnomad4 FIN exome AF: 0.208

Gnomad4 NFE exome AF: 0.257

Gnomad4 OTH exome AF: 0.224

GnomAD4 genome AF: 0.205 AC: 31122 AN: 152146 Hom.: 3563 Cov.: 32 AF XY: 0.201 AC XY: 14922 AN XY: 74390

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.211

Alfa AF: 0.259 Hom.: 5447

Bravo AF: 0.203

Asia WGS AF: 0.150 AC: 523 AN: 3478

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

GeneDx

Aug 20, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.23
Dann	Benign	0.54

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: rs7237; hg19: chr15-85186577;