NM_019045.5:c.1776C>T

Variant names:

• chrX-118432819-C-T
• rs10521584
• NM_019045.5:c.1776C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_019045.5(WDR44):​c.1776C>T​(p.Asn592Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,208,610 control chromosomes in the GnomAD database, including 8,178 homozygotes. There are 52,006 hemizygotes in GnomAD. 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 0.13 (796 hom., 4384 hem., cov: 23)
  • Exomes 𝑓: 0.13 (7382 hom. 47622 hem.)
• Consequence: WDR44 NM_019045.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274
• Publications: 12 publications found

Genes affected

WDR44 (HGNC:30512): (WD repeat domain 44) This gene encodes a protein that interacts with the small GTPase rab11. A similar protein in rat binds the GTP-containing active form of rab11. This protein may play a role in endosome recycling. Alternate splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.173).
• BP7: Synonymous conserved (PhyloP=-0.274 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR44	NM_019045.5	c.1776C>T	p.Asn592Asn	synonymous_variant	Exon 13 of 20	ENST00000254029.8	NP_061918.3
WDR44	NM_001184965.2	c.1776C>T	p.Asn592Asn	synonymous_variant	Exon 13 of 20		NP_001171894.1
WDR44	NM_001184966.1	c.1701C>T	p.Asn567Asn	synonymous_variant	Exon 12 of 18		NP_001171895.1
WDR44	XM_011531353.4	c.1701C>T	p.Asn567Asn	synonymous_variant	Exon 12 of 19		XP_011529655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR44	ENST00000254029.8	c.1776C>T	p.Asn592Asn	synonymous_variant	Exon 13 of 20	1	NM_019045.5	ENSP00000254029.3
WDR44	ENST00000371825.7	c.1776C>T	p.Asn592Asn	synonymous_variant	Exon 13 of 20	1		ENSP00000360890.3
WDR44	ENST00000371848.3	c.1473C>T	p.Asn491Asn	synonymous_variant	Exon 10 of 18	1		ENSP00000360914.3
WDR44	ENST00000371822.9	c.1701C>T	p.Asn567Asn	synonymous_variant	Exon 12 of 18	2		ENSP00000360887.5

Frequencies

GnomAD3 genomes AF: 0.131 AC: 14601 AN: 111683 Hom.: 786 Cov.: 23

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0796

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.160

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.141

GnomAD2 exomes AF: 0.171 AC: 31281 AN: 183148 AF XY: 0.160

Gnomad AFR exome AF: 0.105

Gnomad AMR exome AF: 0.382

Gnomad ASJ exome AF: 0.126

Gnomad EAS exome AF: 0.189

Gnomad FIN exome AF: 0.120

Gnomad NFE exome AF: 0.122

Gnomad OTH exome AF: 0.162

GnomAD4 exome AF: 0.131 AC: 143640 AN: 1096874 Hom.: 7382 Cov.: 30 AF XY: 0.131 AC XY: 47622 AN XY: 362992

African (AFR) AF: 0.106 AC: 2800 AN: 26392

American (AMR) AF: 0.373 AC: 13128 AN: 35161

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 2455 AN: 19372

East Asian (EAS) AF: 0.179 AC: 5407 AN: 30191

South Asian (SAS) AF: 0.166 AC: 8981 AN: 54074

European-Finnish (FIN) AF: 0.120 AC: 4849 AN: 40525

Middle Eastern (MID) AF: 0.122 AC: 503 AN: 4134

European-Non Finnish (NFE) AF: 0.118 AC: 99211 AN: 840989

Other (OTH) AF: 0.137 AC: 6306 AN: 46036

GnomAD4 genome AF: 0.131 AC: 14630 AN: 111736 Hom.: 796 Cov.: 23 AF XY: 0.129 AC XY: 4384 AN XY: 33936

African (AFR) AF: 0.108 AC: 3319 AN: 30839

American (AMR) AF: 0.256 AC: 2692 AN: 10521

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 324 AN: 2645

East Asian (EAS) AF: 0.175 AC: 617 AN: 3534

South Asian (SAS) AF: 0.159 AC: 429 AN: 2695

European-Finnish (FIN) AF: 0.117 AC: 705 AN: 6024

Middle Eastern (MID) AF: 0.157 AC: 34 AN: 217

European-Non Finnish (NFE) AF: 0.118 AC: 6237 AN: 53058

Other (OTH) AF: 0.144 AC: 219 AN: 1525

Alfa AF: 0.135 Hom.: 6538

Bravo AF: 0.148

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	1.4
DANN	Benign	0.66
PhyloP100		-0.27
Mutation Taster		=85/15	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: rs10521584; hg19: chrX-117566782; COSMIC: COSV54159816;