Variant chr9-132618386-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022779.9(DDX31):c.1769C>T(p.Thr590Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000955 in 1,612,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000095 ( 0 hom. )

Consequence

DDX31
NM_022779.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.19

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:

DDX31 (HGNC:):

DDX31 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.249248).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX31	NM_022779.9 linkuse as main transcript	c.1769C>T	p.Thr590Met	missense_variant	18/20	ENST00000372159.8	NP_073616.7	Q9H8H2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX31	ENST00000372159.8 linkuse as main transcript	c.1769C>T	p.Thr590Met	missense_variant	18/20	1	NM_022779.9	ENSP00000361232.4		Q9H8H2

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152160

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000152

AC:

AN:

249260

Hom.:

AF XY:

0.000156

AC XY:

AN XY:

134642

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000164

Gnomad SAS exome

AF:

0.0000334

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.000229

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.0000952

AC:

139

AN:

1459924

Hom.:

Cov.:

AF XY:

0.0000854

AC XY:

AN XY:

726168

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000234

Gnomad4 FIN exome

AF:

0.000281

Gnomad4 NFE exome

AF:

0.0000981

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.0000986

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000124

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.000173

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000179

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 17, 2021

The c.2084C>T (p.T695M) alteration is located in exon 18 (coding exon 18) of the DDX31 gene. This alteration results from a C to T substitution at nucleotide position 2084, causing the threonine (T) at amino acid position 695 to be replaced by a methionine (M). 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

0.093

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0078

T;T;.

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.83

.;T;T

M_CAP

Uncertain

0.086

MetaRNN

Benign

0.25

T;T;T

MetaSVM

Benign

-0.67

MutationAssessor

Benign

0.98

L;L;.

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.5

N;.;.

REVEL

Benign

0.21

Sift

Benign

0.24

T;.;.

Sift4G

Benign

0.24

T;T;T

Polyphen

0.98

D;D;.

Vest4

0.78

MVP

0.57

MPC

0.24

ClinPred

0.063

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.022

gMVP

0.54

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