11-125908410-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_013264.5(DDX25):​c.414C>G​(p.Asn138Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N138N) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DDX25 NM_013264.5 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.767

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>G	p.Asn138Lys	missense	Exon 6 of 12	NP_037396.3
	DDX25	NM_001330438.2		c.72C>G	p.Asn24Lys	missense	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>G	p.Asn138Lys	missense	Exon 6 of 12	ENSP00000263576.6	Q9UHL0-1
	DDX25	ENST00000530414.5	TSL:2	c.423C>G	p.Asn141Lys	missense	Exon 6 of 11	ENSP00000463333.1	J3QL17
	DDX25	ENST00000942563.1		c.414C>G	p.Asn138Lys	missense	Exon 6 of 12	ENSP00000612622.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 20

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Benign	0.86
DEOGEN2	Uncertain	0.42	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.097
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.080	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.67	T
MutationAssessor	Pathogenic	3.7	H
PhyloP100		0.34
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-5.9	D
REVEL	Benign	0.22
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.24	B
Vest4		0.78
MutPred		0.75		Gain of methylation at N138 (P = 0.0051)
MVP		0.32
MPC		0.76
ClinPred		0.98	D
GERP RS		2.3
Varity_R		0.96
gMVP		0.87
Mutation Taster		=37/63	disease causing

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;