rs8179021

Variant names:

• chrY-12906671-C-T
• rs8179021
• NM_004660.5:c.46-866C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004660.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX3Y	NM_004660.5	MANE Select	c.46-866C>T		intron	N/A	NP_004651.2
	DDX3Y	NM_001122665.3		c.46-866C>T		intron	N/A	NP_001116137.1
	DDX3Y	NM_001302552.3		c.36+856C>T		intron	N/A	NP_001289481.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX3Y	ENST00000336079.8	TSL:1 MANE Select	c.46-866C>T		intron	N/A	ENSP00000336725.3
	DDX3Y	ENST00000360160.8	TSL:1	c.46-866C>T		intron	N/A	ENSP00000353284.4
	DDX3Y	ENST00000440554.1	TSL:3	c.36+856C>T		intron	N/A	ENSP00000400377.1

Frequencies

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

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

African (AFR) AF: 0.00483 AC: 41 AN: 8480

American (AMR) AF: 0.117 AC: 419 AN: 3591

Ashkenazi Jewish (ASJ) AF: 0.0324 AC: 25 AN: 771

East Asian (EAS) AF: 0.0133 AC: 17 AN: 1279

South Asian (SAS) AF: 0.0246 AC: 36 AN: 1463

European-Finnish (FIN) AF: 0.000303 AC: 1 AN: 3301

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 72

European-Non Finnish (NFE) AF: 0.00371 AC: 50 AN: 13476

Other (OTH) AF: 0.0131 AC: 6 AN: 457

Alfa AF: 0.0446 Hom.: 1733

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.2
DANN	Benign	0.58
PhyloP100		-0.86
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs8179021; hg19: chrY-15018582;