rs2032624

Positions:

• chrY-12914512-C-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004660.5(DDX3Y):​c.674-52C>A 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 0.60 (0 hom., 19639 hem., cov: 0)
  • Exomes 𝑓: 0.48 (0 hom. 118804 hem.)
  • Failed GnomAD Quality Control
• Consequence: DDX3Y NM_004660.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0700

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX3Y	NM_004660.5	c.674-52C>A		intron_variant		ENST00000336079.8	NP_004651.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX3Y	ENST00000336079.8	c.674-52C>A		intron_variant		1	NM_004660.5	ENSP00000336725	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 19565 AN: 32611 Hom.: 0 Cov.: 0 AF XY: 0.600 AC XY: 19565 AN XY: 32611 FAILED QC

Gnomad AFR AF: 0.799

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.813

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.939

Gnomad MID AF: 0.960

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.566

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.482 AC: 118804 AN: 246397 Hom.: 0 Cov.: 0 AF XY: 0.482 AC XY: 118804 AN XY: 246397

Gnomad4 AFR exome AF: 0.847

Gnomad4 AMR exome AF: 0.590

Gnomad4 ASJ exome AF: 0.805

Gnomad4 EAS exome AF: 0.998

Gnomad4 SAS exome AF: 0.644

Gnomad4 FIN exome AF: 0.914

Gnomad4 NFE exome AF: 0.360

Gnomad4 OTH exome AF: 0.535

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.601 AC: 19639 AN: 32675 Hom.: 0 Cov.: 0 AF XY: 0.601 AC XY: 19639 AN XY: 32675

Gnomad4 AFR AF: 0.800

Gnomad4 AMR AF: 0.506

Gnomad4 ASJ AF: 0.813

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.657

Gnomad4 FIN AF: 0.939

Gnomad4 NFE AF: 0.369

Gnomad4 OTH AF: 0.574

Alfa AF: 0.411 Hom.: 18416

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2032624; hg19: chrY-15026424;