rs8179021

Positions:

• chrY-12906671-C-T

Variant summary

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

The NM_004660.5(DDX3Y):​c.46-866C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.018 (0 hom., 595 hem., cov: 0)
• Consequence: DDX3Y NM_004660.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.860

Genes affected

DDX3Y (HGNC:2699): (DEAD-box helicase 3 Y-linked) The protein encoded by this gene is a member of the DEAD-box RNA helicase family, characterized by nine conserved motifs, included the conserved Asp-Glu-Ala-Asp (DEAD) motif. These motifs are thought to be involved in ATP binding, hydrolysis, RNA binding, and in the formation of intramolecular interactions. This protein shares high similarity to DDX3X, on the X chromosome, but a deletion of this gene is not complemented by DDX3X. Mutations in this gene result in male infertility, a reduction in germ cell numbers, and can result in Sertoli-cell only sydrome. Pseudogenes sharing similarity to both this gene and the DDX3X paralog are found on chromosome 4 and the X chromosome. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX3Y	NM_004660.5	c.46-866C>T		intron_variant		ENST00000336079.8	NP_004651.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX3Y	ENST00000336079.8	c.46-866C>T		intron_variant		1	NM_004660.5	ENSP00000336725	P1

Frequencies

GnomAD3 genomes AF: 0.0177 AC: 585 AN: 33044 Hom.: 0 Cov.: 0 AF XY: 0.0177 AC XY: 585 AN XY: 33044

Gnomad AFR AF: 0.00486

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0324

Gnomad EAS AF: 0.0133

Gnomad SAS AF: 0.0240

Gnomad FIN AF: 0.000303

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00371

Gnomad OTH AF: 0.0132

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

GnomAD4 genome AF: 0.0180 AC: 595 AN: 33105 Hom.: 0 Cov.: 0 AF XY: 0.0180 AC XY: 595 AN XY: 33105

Gnomad4 AFR AF: 0.00483

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.0324

Gnomad4 EAS AF: 0.0133

Gnomad4 SAS AF: 0.0246

Gnomad4 FIN AF: 0.000303

Gnomad4 NFE AF: 0.00371

Gnomad4 OTH AF: 0.0131

Alfa AF: 0.0294 Hom.: 627

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.2
DANN	Benign	0.58

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: rs8179021; hg19: chrY-15018582;