11-125908410-C-T

Variant names:

• chr11-125908410-C-T
• rs34007659
• NM_013264.5:c.414C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_013264.5(DDX25):​c.414C>T​(p.Asn138Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0028 in 1,613,944 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (66 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (60 hom.)
• Consequence: DDX25 NM_013264.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.337
• Publications: 2 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.025).
• BP6: Variant 11-125908410-C-T is Benign according to our data. Variant chr11-125908410-C-T is described in ClinVar as Benign. ClinVar VariationId is 768496.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.337 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0501 is higher than 0.05.

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.414C>T	p.Asn138Asn	synonymous	Exon 6 of 12	NP_037396.3
	DDX25	NM_001330438.2		c.72C>T	p.Asn24Asn	synonymous	Exon 6 of 12	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.414C>T	p.Asn138Asn	synonymous	Exon 6 of 12	ENSP00000263576.6	Q9UHL0-1
	DDX25	ENST00000530414.5	TSL:2	c.423C>T	p.Asn141Asn	synonymous	Exon 6 of 11	ENSP00000463333.1	J3QL17
	DDX25	ENST00000942563.1		c.414C>T	p.Asn138Asn	synonymous	Exon 6 of 12	ENSP00000612622.1

Frequencies

GnomAD3 genomes AF: 0.0149 AC: 2261 AN: 152134 Hom.: 67 Cov.: 32

Gnomad AFR AF: 0.0519

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.00390 AC: 972 AN: 249244 AF XY: 0.00306

Gnomad AFR exome AF: 0.0564

Gnomad AMR exome AF: 0.00185

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000221

Gnomad OTH exome AF: 0.000826

GnomAD4 exome AF: 0.00154 AC: 2253 AN: 1461692 Hom.: 60 Cov.: 33 AF XY: 0.00128 AC XY: 932 AN XY: 727124

African (AFR) AF: 0.0543 AC: 1818 AN: 33480

American (AMR) AF: 0.00239 AC: 107 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5766

European-Non Finnish (NFE) AF: 0.000110 AC: 122 AN: 1111860

Other (OTH) AF: 0.00305 AC: 184 AN: 60372

GnomAD4 genome AF: 0.0149 AC: 2269 AN: 152252 Hom.: 66 Cov.: 32 AF XY: 0.0144 AC XY: 1073 AN XY: 74444

African (AFR) AF: 0.0519 AC: 2156 AN: 41514

American (AMR) AF: 0.00451 AC: 69 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68026

Other (OTH) AF: 0.0113 AC: 24 AN: 2116

Alfa AF: 0.00572 Hom.: 20

Bravo AF: 0.0170

Asia WGS AF: 0.00404 AC: 15 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	9.0
DANN	Benign	0.74
PhyloP100		0.34
Mutation Taster		=91/9	polymorphism (auto)

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: rs34007659; hg19: chr11-125778305;