chr11-125906472-C-T

Variant names:

• chr11-125906472-C-T
• rs78086532
• NM_013264.5:c.311+263C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_013264.5(DDX25):​c.311+263C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 151,706 control chromosomes in the GnomAD database, including 3,281 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.19 (3281 hom., cov: 28)
• Consequence: DDX25 NM_013264.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.19
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 11-125906472-C-T is Benign according to our data. Variant chr11-125906472-C-T is described in ClinVar as Benign. ClinVar VariationId is 1258301.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.251 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.311+263C>T		intron	N/A	NP_037396.3
	DDX25	NM_001330438.2		c.-32+263C>T		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.311+263C>T		intron	N/A	ENSP00000263576.6	Q9UHL0-1
	DDX25	ENST00000530414.5	TSL:2	c.320+263C>T		intron	N/A	ENSP00000463333.1	J3QL17
	DDX25	ENST00000942563.1		c.311+263C>T		intron	N/A	ENSP00000612622.1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29199 AN: 151588 Hom.: 3282 Cov.: 28

Gnomad AFR AF: 0.0799

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.200

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.193 AC: 29204 AN: 151706 Hom.: 3281 Cov.: 28 AF XY: 0.191 AC XY: 14172 AN XY: 74126

African (AFR) AF: 0.0797 AC: 3303 AN: 41428

American (AMR) AF: 0.205 AC: 3125 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 731 AN: 3466

East Asian (EAS) AF: 0.182 AC: 929 AN: 5106

South Asian (SAS) AF: 0.150 AC: 720 AN: 4792

European-Finnish (FIN) AF: 0.245 AC: 2575 AN: 10504

Middle Eastern (MID) AF: 0.200 AC: 58 AN: 290

European-Non Finnish (NFE) AF: 0.254 AC: 17220 AN: 67864

Other (OTH) AF: 0.199 AC: 420 AN: 2106

Alfa AF: 0.114 Hom.: 214

Bravo AF: 0.187

Asia WGS AF: 0.159 AC: 556 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.47
DANN	Benign	0.57
PhyloP100		-1.2
PromoterAI		0.018	Neutral
Mutation Taster		=100/0	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: rs78086532; hg19: chr11-125776367;