Genetic Variant DDX31:p.Ala575Thr (chr9-132618432-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022779.9(DDX31):c.1723G>A(p.Ala575Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A575S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DDX31
NM_022779.9 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.795

Publications

0 publications found

Variant links:

Genes affected

DDX31 (HGNC:16715): (DEAD-box helicase 31) 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 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 function of this member has not been determined. Alternative splicing of this gene generates multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2016]

DDX31 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09872919).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022779.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DDX31	NM_022779.9	MANE Select	c.1723G>A	p.Ala575Thr	missense	Exon 18 of 20	NP_073616.7
DDX31	NM_001322341.2		c.1750G>A	p.Ala584Thr	missense	Exon 19 of 21	NP_001309270.1
DDX31	NM_001322343.1		c.1651G>A	p.Ala551Thr	missense	Exon 18 of 20	NP_001309272.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DDX31	ENST00000372159.8	TSL:1 MANE Select	c.1723G>A	p.Ala575Thr	missense	Exon 18 of 20	ENSP00000361232.4	Q9H8H2-5
DDX31	ENST00000893393.1		c.1867G>A	p.Ala623Thr	missense	Exon 19 of 21	ENSP00000563452.1
DDX31	ENST00000893391.1		c.1681G>A	p.Ala561Thr	missense	Exon 17 of 19	ENSP00000563450.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457712

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725022

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33378

American (AMR)

AF:

0.00

AC:

AN:

43970

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26108

East Asian (EAS)

AF:

0.00

AC:

AN:

39502

South Asian (SAS)

AF:

0.00

AC:

AN:

85138

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

9.01e-7

AC:

AN:

1110204

Other (OTH)

AF:

0.00

AC:

AN:

60260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.018

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.77

M_CAP

Benign

0.013

MetaRNN

Benign

0.099

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.0

PhyloP100

0.80

PrimateAI

Benign

0.28

PROVEAN

Benign

0.090

REVEL

Benign

0.032

Sift

Benign

0.27

Sift4G

Benign

0.55

Polyphen

0.38

Vest4

0.21

MutPred

0.26

Gain of phosphorylation at A680 (P = 0.0478)

MVP

0.44

MPC

0.15

ClinPred

0.14

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.029

gMVP

0.38

Mutation Taster

=82/18

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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