Variant 5-134817701-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001300860.2(DDX46):c.2819A>G(p.Asn940Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DDX46
NM_001300860.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.26

Variant links:

Genes affected

DDX46 (HGNC:18681): (DEAD-box helicase 46) This gene encodes a member of the DEAD box protein family. 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. The protein encoded by this gene is a component of the 17S U2 snRNP complex; it plays an important role in pre-mRNA splicing. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2014]

DDX46 links:

DDX46 (HGNC:):

DDX46 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.846

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX46	NM_001300860.2 linkuse as main transcript	c.2819A>G	p.Asn940Ser	missense_variant	20/23	ENST00000452510.7	NP_001287789.1	Q7L014A0A0C4DG89
DDX46	NM_014829.4 linkuse as main transcript	c.2816A>G	p.Asn939Ser	missense_variant	20/23		NP_055644.2	Q7L014
DDX46	NR_125341.2 linkuse as main transcript	n.2952A>G		non_coding_transcript_exon_variant	20/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DDX46	ENST00000452510.7 linkuse as main transcript	c.2819A>G	p.Asn940Ser	missense_variant	20/23	1	NM_001300860.2	ENSP00000416534.2	A0A0C4DG89
DDX46	ENST00000507392.5 linkuse as main transcript	n.*1376A>G		non_coding_transcript_exon_variant	20/23	2		ENSP00000427290.1	D6RJA6
DDX46	ENST00000507392.5 linkuse as main transcript	n.*1376A>G		3_prime_UTR_variant	20/23	2		ENSP00000427290.1	D6RJA6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461616

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727066

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:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Autism;C0030421:Paraganglioma;C0031511:Pheochromocytoma;C0241240:Tall stature;C0557874:Global developmental delay;C0848558:Hypospadias

Uncertain:1

Uncertain significance, criteria provided, single submitter

research

HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology

Oct 14, 2021

ACMG codes: PM2, PP3 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Benign

-0.061

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.45

.;T

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

1.0

D;D

M_CAP

Uncertain

0.23

MetaRNN

Pathogenic

0.85

D;D

MetaSVM

Uncertain

0.19

MutationAssessor

Uncertain

2.8

.;M

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-4.8

D;D

REVEL

Uncertain

0.55

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

.;D

Vest4

0.87

MutPred

0.18

.;Gain of phosphorylation at N939 (P = 0.0512);

MVP

0.92

MPC

2.3

ClinPred

1.0

GERP RS

3.4

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Varity_R

0.74

gMVP

0.99

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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