rs2032590

Variant names:

• chrY-12907702-T-G
• rs2032590
• NM_004660.5:c.103+108T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DDX3Y	NM_004660.5	c.103+108T>G		intron_variant	Intron 2 of 16	ENST00000336079.8	NP_004651.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX3Y	ENST00000336079.8	c.103+108T>G		intron_variant	Intron 2 of 16	1	NM_004660.5	ENSP00000336725.3

Frequencies

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

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

African (AFR) AF: 0.291 AC: 660 AN: 2267

American (AMR) AF: 0.00508 AC: 15 AN: 2950

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2555

East Asian (EAS) AF: 0.00 AC: 0 AN: 5881

South Asian (SAS) AF: 0.00105 AC: 7 AN: 6673

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 383

European-Non Finnish (NFE) AF: 0.000276 AC: 14 AN: 50691

Other (OTH) AF: 0.0112 AC: 47 AN: 4209

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

African (AFR) AF: 0.227 AC: 1935 AN: 8524

American (AMR) AF: 0.0103 AC: 39 AN: 3777

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 771

East Asian (EAS) AF: 0.00 AC: 0 AN: 1332

South Asian (SAS) AF: 0.000643 AC: 1 AN: 1556

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3470

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 74

European-Non Finnish (NFE) AF: 0.00102 AC: 14 AN: 13670

Other (OTH) AF: 0.0387 AC: 18 AN: 465

Alfa AF: 0.0782 Hom.: 2163

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
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs2032590; hg19: chrY-15019613;