Y-12915726-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_004660.5(DDX3Y):c.1116C>T(p.Gly372=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00090 (0 hom., 30 hem., cov: 0)
  • Exomes 𝑓: 0.0014 (0 hom. 526 hem.)
• Consequence: DDX3Y NM_004660.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.13

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant Y-12915726-C-T is Benign according to our data. Variant chrY-12915726-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3044219.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.13 with no splicing effect.
• BS2: High Hemizygotes in GnomAd at 30 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX3Y	NM_004660.5	c.1116C>T	p.Gly372=	synonymous_variant	11/17	ENST00000336079.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX3Y	ENST00000336079.8	c.1116C>T	p.Gly372=	synonymous_variant	11/17	1	NM_004660.5	P1
DDX3Y	ENST00000360160.8	c.1116C>T	p.Gly372=	synonymous_variant	12/18	1		P1
DDX3Y	ENST00000495478.1	n.231C>T		non_coding_transcript_exon_variant	1/3	4

Frequencies

GnomAD3 genomes AF: 0.000897 AC: 30 AN: 33447 Hom.: 0 Cov.: 0 AF XY: 0.000897 AC XY: 30 AN XY: 33447

Gnomad AFR AF: 0.000936

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00163

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000825 AC: 56 AN: 67855 Hom.: 0 AF XY: 0.000825 AC XY: 56 AN XY: 67855

Gnomad AFR exome AF: 0.000323

Gnomad AMR exome AF: 0.000140

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000177

Gnomad NFE exome AF: 0.00167

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00145 AC: 526 AN: 363071 Hom.: 0 Cov.: 15 AF XY: 0.00145 AC XY: 526 AN XY: 363071

Gnomad4 AFR exome AF: 0.000283

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000155

Gnomad4 NFE exome AF: 0.00189

Gnomad4 OTH exome AF: 0.000911

GnomAD4 genome AF: 0.000895 AC: 30 AN: 33511 Hom.: 0 Cov.: 0 AF XY: 0.000895 AC XY: 30 AN XY: 33511

Gnomad4 AFR AF: 0.000930

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00163

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0922 Hom.: 1089

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

DDX3Y-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 07, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	2.5
Dann	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs201495354; hg19: chrY-15027638;