Variant chr12-31078517-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_030653.4(DDX11):c.124T>C(p.Phe42Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DDX11
NM_030653.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.33

Variant links:

Genes affected

DDX11 (HGNC:2736): (DEAD/H-box helicase 11) 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 this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which is an enzyme that possesses both ATPase and DNA helicase activities. This gene is a homolog of the yeast CHL1 gene, and may function to maintain chromosome transmission fidelity and genome stability. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

DDX11 links:

DDX11 (HGNC:):

DDX11 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX11	NM_030653.4 linkuse as main transcript	c.124T>C	p.Phe42Leu	missense_variant	2/27	ENST00000542838.6	NP_085911.2	Q2NKM7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX11	ENST00000542838.6 linkuse as main transcript	c.124T>C	p.Phe42Leu	missense_variant	2/27	1	NM_030653.4	ENSP00000443426.1		Q96FC9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.85e-7

AC:

AN:

1459630

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726118

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 16, 2024

The c.124T>C (p.F42L) alteration is located in exon 2 (coding exon 1) of the DDX11 gene. This alteration results from a T to C substitution at nucleotide position 124, causing the phenylalanine (F) at amino acid position 42 to be replaced by a leucine (L). 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

Pathogenic

0.97

BayesDel_addAF

Benign

-0.014

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

.;.;T;.;T;.;.

Eigen

Benign

0.14

Eigen_PC

Benign

0.072

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.97

D;D;D;D;D;D;D

M_CAP

Benign

0.023

MetaRNN

Uncertain

0.44

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-5.4

D;D;D;D;D;D;D

REVEL

Benign

0.25

Sift

Pathogenic

0.0

D;D;D;D;D;D;T

Sift4G

Uncertain

0.018

D;D;D;D;D;D;T

Polyphen

0.99

D;.;.;.;D;D;.

Vest4

0.66

MutPred

0.36

Gain of catalytic residue at F42 (P = 0);.;Gain of catalytic residue at F42 (P = 0);.;Gain of catalytic residue at F42 (P = 0);Gain of catalytic residue at F42 (P = 0);.;

MVP

0.31

ClinPred

0.99

GERP RS

3.2

Varity_R

0.50

gMVP

0.82

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over