11-125904566-C-A

Variant names:

• chr11-125904566-C-A
• rs762319891
• NM_013264.5:c.49C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4 BP7

The NM_013264.5(DDX25):​c.49C>A​(p.Arg17Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000224 in 1,340,758 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: DDX25 NM_013264.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310
• Publications: 0 publications found

Genes affected

DDX25 (HGNC:18698): (DEAD-box helicase 25) DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure, such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of the DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a member of this family. The encoded protein is a gonadotropin-regulated and developmentally expressed testicular RNA helicase. It may serve to maintain testicular functions related to steroidogenesis and spermatogenesis. [provided by RefSeq, Jul 2008]

DDX25 Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center

DDX25-AS1 (HGNC:58188):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.11).
• BP7: Synonymous conserved (PhyloP=-0.031 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013264.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX25	NM_013264.5	MANE Select	c.49C>A	p.Arg17Arg	synonymous	Exon 1 of 12	NP_037396.3
	DDX25	NM_001330438.2		c.-279-646C>A		intron	N/A	NP_001317367.1	A0A384NYS3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX25	ENST00000263576.11	TSL:1 MANE Select	c.49C>A	p.Arg17Arg	synonymous	Exon 1 of 12	ENSP00000263576.6	Q9UHL0-1
	DDX25	ENST00000530414.5	TSL:2	c.58C>A	p.Arg20Arg	synonymous	Exon 1 of 11	ENSP00000463333.1	J3QL17
	DDX25	ENST00000942563.1		c.49C>A	p.Arg17Arg	synonymous	Exon 1 of 12	ENSP00000612622.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000224 AC: 3 AN: 1340758 Hom.: 0 Cov.: 30 AF XY: 0.00000304 AC XY: 2 AN XY: 657476

African (AFR) AF: 0.00 AC: 0 AN: 29400

American (AMR) AF: 0.00 AC: 0 AN: 29016

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22010

East Asian (EAS) AF: 0.00 AC: 0 AN: 33612

South Asian (SAS) AF: 0.0000139 AC: 1 AN: 71946

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41660

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3952

European-Non Finnish (NFE) AF: 9.49e-7 AC: 1 AN: 1053720

Other (OTH) AF: 0.0000180 AC: 1 AN: 55442

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.11
CADD	Benign	15
DANN	Benign	0.95
PhyloP100		-0.031
PromoterAI		-0.045	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs762319891; hg19: chr11-125774461;