Variant Y-12915726-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2

The NM_004660.5(DDX3Y):c.1116C>T(p.Gly372Gly) 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 (no stars).

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

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.13

Variant links:

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]

DDX3Y links:

DDX3Y (HGNC:):

DDX3Y links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 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 no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-1.13 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 30 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX3Y	NM_004660.5 linkuse as main transcript	c.1116C>T	p.Gly372Gly	synonymous_variant	11/17	ENST00000336079.8	NP_004651.2	O15523-1A0A024R9A4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DDX3Y	ENST00000336079.8 linkuse as main transcript	c.1116C>T	p.Gly372Gly	synonymous_variant	11/17	1	NM_004660.5	ENSP00000336725.3	O15523-1
DDX3Y	ENST00000360160.8 linkuse as main transcript	c.1116C>T	p.Gly372Gly	synonymous_variant	12/18	1		ENSP00000353284.4	O15523-1
DDX3Y	ENST00000495478.1 linkuse as main transcript	n.231C>T		non_coding_transcript_exon_variant	1/3	4

Frequencies

GnomAD3 genomes

AF:

0.000897

AC:

AN:

33447

Hom.:

Cov.:

AF XY:

0.000897

AC XY:

AN XY:

33447

show subpopulations

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:

AN:

67855

Hom.:

AF XY:

0.000825

AC XY:

AN XY:

67855

show subpopulations

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.:

Cov.:

AF XY:

0.00145

AC XY:

526

AN XY:

363071

show subpopulations

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:

AN:

33511

Hom.:

Cov.:

AF XY:

0.000895

AC XY:

AN XY:

33511

show subpopulations

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: no assertion criteria provided

LINK: link

Submissions by phenotype

DDX3Y-related disorder

Benign:1

Likely benign, no assertion criteria provided

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over