Genetic Variant NM_030653.4:c.-195T>A (chr12-31073901-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_030653.4(DDX11):c.-195T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 152,182 control chromosomes in the GnomAD database, including 22,686 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.53 ( 22685 hom., cov: 33)

Exomes 𝑓: 0.35 ( 1 hom. )

Consequence

DDX11
NM_030653.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0320

Publications

21 publications found

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-AS1 (HGNC:44176): (DDX11 antisense RNA 1)

DDX11-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030653.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DDX11	NM_030653.4	MANE Select	c.-195T>A	5_prime_UTR	Exon 1 of 27	NP_085911.2	Q96FC9-2
DDX11	NM_001257144.2		c.-73T>A	5_prime_UTR	Exon 1 of 27	NP_001244073.1	Q96FC9-1
DDX11	NM_152438.2		c.-195T>A	5_prime_UTR	Exon 1 of 27	NP_689651.1	Q96FC9-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DDX11	ENST00000542838.6	TSL:1 MANE Select	c.-195T>A	5_prime_UTR	Exon 1 of 27	ENSP00000443426.1	Q96FC9-2
DDX11	ENST00000545668.5	TSL:1	c.-73T>A	5_prime_UTR	Exon 1 of 27	ENSP00000440402.1	Q96FC9-1
DDX11	ENST00000228264.10	TSL:1	c.-78T>A	5_prime_UTR	Exon 1 of 27	ENSP00000228264.6	Q96FC9-3

Frequencies

GnomAD3 genomes

AF:

0.532

AC:

80891

AN:

152044

Hom.:

22631

Cov.:

show subpopulations

Gnomad AFR

AF:

0.658

Gnomad AMI

AF:

0.457

Gnomad AMR

AF:

0.593

Gnomad ASJ

AF:

0.386

Gnomad EAS

AF:

0.816

Gnomad SAS

AF:

0.570

Gnomad FIN

AF:

0.418

Gnomad MID

AF:

0.437

Gnomad NFE

AF:

0.444

Gnomad OTH

AF:

0.515

GnomAD4 exome

AF:

0.350

AC:

AN:

Hom.:

Cov.:

AF XY:

0.375

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.333

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.532

AC:

81000

AN:

152162

Hom.:

22685

Cov.:

AF XY:

0.535

AC XY:

39784

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.659

AC:

27347

AN:

41514

American (AMR)

AF:

0.593

AC:

9074

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.386

AC:

1341

AN:

3472

East Asian (EAS)

AF:

0.816

AC:

4224

AN:

5176

South Asian (SAS)

AF:

0.569

AC:

2746

AN:

4824

European-Finnish (FIN)

AF:

0.418

AC:

4424

AN:

10584

Middle Eastern (MID)

AF:

0.435

AC:

128

AN:

294

European-Non Finnish (NFE)

AF:

0.444

AC:

30212

AN:

67974

Other (OTH)

AF:

0.515

AC:

1087

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1893

3787

5680

7574

9467

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

694

1388

2082

2776

3470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.487

Hom.:

2342

Bravo

AF:

0.553

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

6.3

(source)

DANN

Benign

0.65

PhyloP100

-0.032

PromoterAI

-0.67

Under-expression

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over