Variant 11-125904528-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_013264.5(DDX25):c.11T>C(p.Leu4Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000016 in 1,495,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

DDX25
NM_013264.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.80

Variant links:

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 links:

ENSG00000255027 (HGNC:):

ENSG00000255027 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05281213).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX25	NM_013264.5 linkuse as main transcript	c.11T>C	p.Leu4Ser	missense_variant	1/12	ENST00000263576.11	NP_037396.3	Q9UHL0-1
DDX25	XM_047426849.1 linkuse as main transcript	c.11T>C	p.Leu4Ser	missense_variant	1/11		XP_047282805.1
DDX25	NM_001330438.2 linkuse as main transcript	c.-279-684T>C		intron_variant			NP_001317367.1	Q9UHL0-2A0A384NYS3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX25	ENST00000263576.11 linkuse as main transcript	c.11T>C	p.Leu4Ser	missense_variant	1/12	1	NM_013264.5	ENSP00000263576.6		Q9UHL0-1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000731

AC:

AN:

95712

Hom.:

AF XY:

0.0000582

AC XY:

AN XY:

51588

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000813

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000127

AC:

AN:

1343242

Hom.:

Cov.:

AF XY:

0.0000121

AC XY:

AN XY:

659096

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000703

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000447

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00136

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000604

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 05, 2023

The c.11T>C (p.L4S) alteration is located in exon 1 (coding exon 1) of the DDX25 gene. This alteration results from a T to C substitution at nucleotide position 11, causing the leucine (L) at amino acid position 4 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

T;T

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.49

T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.053

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.90

L;.

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.57

N;.

REVEL

Benign

0.046

Sift

Uncertain

0.015

D;.

Sift4G

Benign

0.51

T;T

Polyphen

0.0010

B;.

Vest4

0.29

MutPred

0.43

Loss of catalytic residue at L4 (P = 0.0029);.;

MVP

0.16

MPC

0.83

ClinPred

0.16

GERP RS

3.0

Varity_R

0.057

gMVP

0.33

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over