X-118400435-C-T

Position:

• chrX-118400435-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019045.5(WDR44):​c.1274+1965C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 110,731 control chromosomes in the GnomAD database, including 10,830 homozygotes. There are 14,036 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 0.43 (10830 hom., 14036 hem., cov: 22)
• Consequence: WDR44 NM_019045.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.130

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR44	NM_019045.5	c.1274+1965C>T		intron_variant		ENST00000254029.8	NP_061918.3
WDR44	NM_001184965.2	c.1274+1965C>T		intron_variant			NP_001171894.1
WDR44	NM_001184966.1	c.1199+1965C>T		intron_variant			NP_001171895.1
WDR44	XM_011531353.4	c.1199+1965C>T		intron_variant			XP_011529655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR44	ENST00000254029.8	c.1274+1965C>T		intron_variant		1	NM_019045.5	ENSP00000254029.3
WDR44	ENST00000371825.7	c.1274+1965C>T		intron_variant		1		ENSP00000360890.3
WDR44	ENST00000371848.3	c.971+1965C>T		intron_variant		1		ENSP00000360914.3
WDR44	ENST00000371822.9	c.1199+1965C>T		intron_variant		2		ENSP00000360887.5

Frequencies

GnomAD3 genomes AF: 0.434 AC: 48066 AN: 110684 Hom.: 10821 Cov.: 22 AF XY: 0.425 AC XY: 13990 AN XY: 32930

Gnomad AFR AF: 0.863

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.411

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.435 AC: 48126 AN: 110731 Hom.: 10830 Cov.: 22 AF XY: 0.426 AC XY: 14036 AN XY: 32987

Gnomad4 AFR AF: 0.863

Gnomad4 AMR AF: 0.550

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.581

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.417

Alfa AF: 0.209 Hom.: 2962

Bravo AF: 0.491

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.63

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: rs2380316; hg19: chrX-117534398;