17-63787170-G-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong

The NM_203499.3(DDX42):c.121G>T(p.Ala41Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

DDX42
NM_203499.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.94

Variant links:

Genes affected

DDX42 (HGNC:18676): (DEAD-box helicase 42) This gene encodes a member of the Asp-Glu-Ala-Asp (DEAD) box protein family. Members of this protein family are putative RNA helicases, and 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. Members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. Two transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jul 2008]

DDX42 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, DDX42

BP4

Computational evidence support a benign effect (MetaRNN=0.058814913).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DDX42	NM_203499.3 linkuse as main transcript	c.121G>T	p.Ala41Ser	missense_variant	2/18	ENST00000389924.7
DDX42	NM_007372.3 linkuse as main transcript	c.121G>T	p.Ala41Ser	missense_variant	3/19
DDX42	XM_047435281.1 linkuse as main transcript	c.121G>T	p.Ala41Ser	missense_variant	4/20
DDX42	XM_047435282.1 linkuse as main transcript	c.121G>T	p.Ala41Ser	missense_variant	5/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX42	ENST00000389924.7 linkuse as main transcript	c.121G>T	p.Ala41Ser	missense_variant	2/18	5	NM_203499.3	P1	Q86XP3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251442

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

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

Mar 29, 2023

The c.121G>T (p.A41S) alteration is located in exon 3 (coding exon 1) of the DDX42 gene. This alteration results from a G to T substitution at nucleotide position 121, causing the alanine (A) at amino acid position 41 to be replaced by a serine (S). 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

0.077

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.61

Cadd

Benign

Dann

Benign

0.94

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.18

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.83

T;.;.;T

M_CAP

Benign

0.0034

MetaRNN

Benign

0.059

T;T;T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

D;N;N;N;N

PrimateAI

Uncertain

0.49

Sift4G

Benign

0.45

T;T;T;T

Polyphen

0.0080

.;B;B;B

Vest4

0.13, 0.13, 0.13

MutPred

0.12

Gain of phosphorylation at A41 (P = 0.0097);Gain of phosphorylation at A41 (P = 0.0097);Gain of phosphorylation at A41 (P = 0.0097);Gain of phosphorylation at A41 (P = 0.0097);

MVP

0.36

MPC

0.85

ClinPred

0.10

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.038

gMVP

0.12

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