rs2032590

chrY-12907702-T-G

Variant summary

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

The NM_004660.5(DDX3Y):c.103+108T>G 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 0.059 (0 hom., 2007 hem., cov: 0)
  • Exomes 𝑓: 0.0089 (0 hom. 743 hem.)
  • Failed GnomAD Quality Control
• Consequence: DDX3Y NM_004660.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX3Y	NM_004660.5	c.103+108T>G		intron_variant		ENST00000336079.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX3Y	ENST00000336079.8	c.103+108T>G		intron_variant		1	NM_004660.5	P1

Frequencies

GnomAD3 genomes AF: 0.0587 AC: 1984 AN: 33790 Hom.: 0 Cov.: 0 AF XY: 0.0587 AC XY: 1984 AN XY: 33790

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0103

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000644

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00102

Gnomad OTH AF: 0.0390

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00895 AC: 743 AN: 83019 Hom.: 0 AF XY: 0.00895 AC XY: 743 AN XY: 83019

Gnomad4 AFR exome AF: 0.291

Gnomad4 AMR exome AF: 0.00508

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00105

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000276

Gnomad4 OTH exome AF: 0.0112

GnomAD4 genome AF: 0.0593 AC: 2007 AN: 33854 Hom.: 0 Cov.: 0 AF XY: 0.0593 AC XY: 2007 AN XY: 33854

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.0103

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000643

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00102

Gnomad4 OTH AF: 0.0387

Alfa AF: 0.0187 Hom.: 166

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.2
Dann	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2032590; hg19: chrY-15019613;