X-118400435-C-T

Variant names:

• chrX-118400435-C-T
• rs2380316
• NM_019045.5:c.1274+1965C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019045.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR44	NM_019045.5	MANE Select	c.1274+1965C>T		intron	N/A	NP_061918.3
	WDR44	NM_001184965.2		c.1274+1965C>T		intron	N/A	NP_001171894.1	Q5JSH3-2
	WDR44	NM_001184966.1		c.1199+1965C>T		intron	N/A	NP_001171895.1	Q5JSH3-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR44	ENST00000254029.8	TSL:1 MANE Select	c.1274+1965C>T		intron	N/A	ENSP00000254029.3	Q5JSH3-1
	WDR44	ENST00000371825.7	TSL:1	c.1274+1965C>T		intron	N/A	ENSP00000360890.3	Q5JSH3-2
	WDR44	ENST00000371848.3	TSL:1	c.971+1965C>T		intron	N/A	ENSP00000360914.3	H7BY83

Frequencies

GnomAD3 genomes AF: 0.434 AC: 48066 AN: 110684 Hom.: 10821 Cov.: 22

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

African (AFR) AF: 0.863 AC: 26255 AN: 30427

American (AMR) AF: 0.550 AC: 5717 AN: 10398

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 494 AN: 2625

East Asian (EAS) AF: 0.581 AC: 2001 AN: 3447

South Asian (SAS) AF: 0.419 AC: 1103 AN: 2634

European-Finnish (FIN) AF: 0.162 AC: 953 AN: 5889

Middle Eastern (MID) AF: 0.269 AC: 57 AN: 212

European-Non Finnish (NFE) AF: 0.204 AC: 10792 AN: 52911

Other (OTH) AF: 0.417 AC: 632 AN: 1516

Alfa AF: 0.247 Hom.: 4160

Bravo AF: 0.491

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.63
PhyloP100		0.13
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: rs2380316; hg19: chrX-117534398;