rs2032636

chrY-12915617-G-T

Variant summary

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

The NM_004660.5(DDX3Y):c.1020-13G>T variant causes a splice polypyrimidine tract, 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 0.027 (0 hom., 897 hem., cov: 0)
  • Exomes 𝑓: 0.025 (0 hom. 8985 hem.)
• Consequence: DDX3Y NM_004660.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.70

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX3Y	NM_004660.5	c.1020-13G>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000336079.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX3Y	ENST00000336079.8	c.1020-13G>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_004660.5	P1
DDX3Y	ENST00000360160.8	c.1020-13G>T		splice_polypyrimidine_tract_variant, intron_variant		1		P1
DDX3Y	ENST00000495478.1	n.122G>T		non_coding_transcript_exon_variant	1/3	4

Frequencies

GnomAD3 genomes AF: 0.0269 AC: 894 AN: 33295 Hom.: 0 Cov.: 0 AF XY: 0.0269 AC XY: 894 AN XY: 33295

Gnomad AFR AF: 0.00528

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.0593

Gnomad ASJ AF: 0.0810

Gnomad EAS AF: 0.000781

Gnomad SAS AF: 0.0359

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.189

Gnomad NFE AF: 0.0337

Gnomad OTH AF: 0.0344

GnomAD4 exome AF: 0.0249 AC: 8985 AN: 360127 Hom.: 0 Cov.: 4 AF XY: 0.0249 AC XY: 8985 AN XY: 360127

Gnomad4 AFR exome AF: 0.00499

Gnomad4 AMR exome AF: 0.0423

Gnomad4 ASJ exome AF: 0.101

Gnomad4 EAS exome AF: 0.000106

Gnomad4 SAS exome AF: 0.0305

Gnomad4 FIN exome AF: 0.00163

Gnomad4 NFE exome AF: 0.0236

Gnomad4 OTH exome AF: 0.0327

GnomAD4 genome AF: 0.0269 AC: 897 AN: 33359 Hom.: 0 Cov.: 0 AF XY: 0.0269 AC XY: 897 AN XY: 33359

Gnomad4 AFR AF: 0.00525

Gnomad4 AMR AF: 0.0592

Gnomad4 ASJ AF: 0.0810

Gnomad4 EAS AF: 0.000781

Gnomad4 SAS AF: 0.0365

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0339

Gnomad4 OTH AF: 0.0342

Alfa AF: 0.0385 Hom.: 656

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.041

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2032636; hg19: chrY-15027529;