chrY-12915617-G-T

Variant names:

• chrY-12915617-G-T
• rs2032636
• NM_004660.5:c.1020-13G>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.1020-13G>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 0.027 (0 hom., 897 hem., cov: 0)
  • Exomes 𝑓: 0.025 (0 hom. 8985 hem.)
• Consequence: DDX3Y NM_004660.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.70
• Publications: 21 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=-0.98).
• 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 rank	MANE	Protein	UniProt
DDX3Y	NM_004660.5	c.1020-13G>T		intron_variant	Intron 10 of 16	ENST00000336079.8	NP_004651.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX3Y	ENST00000336079.8	c.1020-13G>T		intron_variant	Intron 10 of 16	1	NM_004660.5	ENSP00000336725.3
DDX3Y	ENST00000360160.8	c.1020-13G>T		intron_variant	Intron 11 of 17	1		ENSP00000353284.4
DDX3Y	ENST00000495478.1	n.122G>T		non_coding_transcript_exon_variant	Exon 1 of 3	4

Frequencies

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

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

African (AFR) AF: 0.00499 AC: 35 AN: 7021

American (AMR) AF: 0.0423 AC: 401 AN: 9482

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 681 AN: 6720

East Asian (EAS) AF: 0.000106 AC: 1 AN: 9467

South Asian (SAS) AF: 0.0305 AC: 977 AN: 31984

European-Finnish (FIN) AF: 0.00163 AC: 21 AN: 12864

Middle Eastern (MID) AF: 0.0647 AC: 105 AN: 1623

European-Non Finnish (NFE) AF: 0.0236 AC: 6300 AN: 266776

Other (OTH) AF: 0.0327 AC: 464 AN: 14190

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

African (AFR) AF: 0.00525 AC: 45 AN: 8572

American (AMR) AF: 0.0592 AC: 215 AN: 3631

Ashkenazi Jewish (ASJ) AF: 0.0810 AC: 62 AN: 765

East Asian (EAS) AF: 0.000781 AC: 1 AN: 1280

South Asian (SAS) AF: 0.0365 AC: 56 AN: 1535

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3324

Middle Eastern (MID) AF: 0.192 AC: 14 AN: 73

European-Non Finnish (NFE) AF: 0.0339 AC: 457 AN: 13495

Other (OTH) AF: 0.0342 AC: 16 AN: 468

Alfa AF: 0.0770 Hom.: 762

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
PhyloP100		-4.7

Splicing

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

Other links and lift over

dbSNP: rs2032636; hg19: chrY-15027529;