Variant 2-15621092-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000233084.8(DDX1):c.1423A>C(p.Thr475Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,890 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

DDX1
ENST00000233084.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.74

Variant links:

Genes affected

DDX1 (HGNC:2734): (DEAD-box helicase 1) 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 that acts as an ATP-dependent RNA helicase that has been found to promote coronaviruses replication. [provided by RefSeq, Aug 2021]

DDX1 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
DDX1	NM_004939.3 linkuse as main transcript	c.1423A>C	p.Thr475Pro	missense_variant	18/26	ENST00000233084.8	NP_004930.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX1	ENST00000233084.8 linkuse as main transcript	c.1423A>C	p.Thr475Pro	missense_variant	18/26	1	NM_004939.3	ENSP00000233084	P1	Q92499-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1458890

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

725920

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

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

Aug 15, 2023

The c.1423A>C (p.T475P) alteration is located in exon 18 (coding exon 18) of the DDX1 gene. This alteration results from a A to C substitution at nucleotide position 1423, causing the threonine (T) at amino acid position 475 to be replaced by a proline (P). 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

0.14

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.40

T;T;T;T

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.90

.;D;D;D

M_CAP

Uncertain

0.20

MetaRNN

Uncertain

0.56

D;D;D;D

MetaSVM

Uncertain

0.17

MutationAssessor

Benign

1.9

L;L;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-2.3

N;N;.;.

REVEL

Uncertain

0.54

Sift

Benign

0.12

T;T;.;.

Sift4G

Benign

0.24

T;T;T;T

Polyphen

0.97

D;D;.;.

Vest4

0.60

MutPred

0.32

Loss of phosphorylation at T475 (P = 0.0219);Loss of phosphorylation at T475 (P = 0.0219);.;.;

MVP

0.86

MPC

0.34

ClinPred

0.91

GERP RS

5.8

Varity_R

0.50

gMVP

0.56

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