ENST00000348993.10:n.4854C>T

Variant names:

• chr15-84643346-C-T
• rs7237
• ENST00000348993.10:n.4854C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000348993.10(ENSG00000291159):​n.4854C>T 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 0.235 in 1,218,342 control chromosomes in the GnomAD database, including 35,480 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (3563 hom., cov: 32)
  • Exomes 𝑓: 0.24 (31917 hom.)
• Consequence: ENSG00000291159 ENST00000348993.10 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.68
• Publications: 22 publications found

Genes affected

ENSG00000291159 (HGNC:):

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• 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 rank	MANE	Protein	UniProt
WDR73	NM_032856.5	c.*124G>A		3_prime_UTR_variant	Exon 8 of 8	ENST00000434634.7	NP_116245.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR73	ENST00000434634.7	c.*124G>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_032856.5	ENSP00000387982.3

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

African (AFR) AF: 0.116 AC: 2754 AN: 23804

American (AMR) AF: 0.185 AC: 3993 AN: 21558

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 4600 AN: 17832

East Asian (EAS) AF: 0.0974 AC: 3296 AN: 33846

South Asian (SAS) AF: 0.166 AC: 9756 AN: 58710

European-Finnish (FIN) AF: 0.208 AC: 8176 AN: 39312

Middle Eastern (MID) AF: 0.341 AC: 1081 AN: 3174

European-Non Finnish (NFE) AF: 0.257 AC: 211085 AN: 821822

Other (OTH) AF: 0.224 AC: 10349 AN: 46138

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

African (AFR) AF: 0.118 AC: 4889 AN: 41534

American (AMR) AF: 0.198 AC: 3028 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 893 AN: 3468

East Asian (EAS) AF: 0.107 AC: 557 AN: 5186

South Asian (SAS) AF: 0.144 AC: 694 AN: 4824

European-Finnish (FIN) AF: 0.214 AC: 2262 AN: 10586

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17849 AN: 67962

Other (OTH) AF: 0.211 AC: 444 AN: 2106

Alfa AF: 0.248 Hom.: 7873

Bravo AF: 0.203

Asia WGS AF: 0.150 AC: 523 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 20, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.23
DANN	Benign	0.54
PhyloP100		-1.7
Mutation Taster		=100/0	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: rs7237; hg19: chr15-85186577;