Genetic Variant DDX19B:p.Asn417Ser (chr16-70333031-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_007242.7(DDX19B):c.1250A>G(p.Asn417Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

DDX19B
NM_007242.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.91

Variant links:

Genes affected

DDX19B (HGNC:2742): (DEAD-box helicase 19B) 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, which exhibits RNA-dependent ATPase and ATP-dependent RNA-unwinding activities. This protein is recruited to the cytoplasmic fibrils of the nuclear pore complex, where it participates in the export of mRNA from the nucleus. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

DDX19B links:

ENSG00000260537 (HGNC:):

ENSG00000260537 links:

DDX19A-DT (HGNC:55349): (DDX19A divergent transcript)

DDX19A-DT links:

Genome browser will be placed here

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=0.09514359).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX19B	NM_007242.7 link	c.1250A>G	p.Asn417Ser	missense_variant	Exon 11 of 12	ENST00000288071.11	NP_009173.1	Q9UMR2-1A0A0U4B4U6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX19B	ENST00000288071.11 link	c.1250A>G	p.Asn417Ser	missense_variant	Exon 11 of 12	1	NM_007242.7	ENSP00000288071.7		Q9UMR2-1
ENSG00000260537	ENST00000443119.7 link	c.160+18076A>G		intron_variant	Intron 3 of 11	5		ENSP00000399208.3		F6QDS0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

250962

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135634

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.00000479

AC:

AN:

1461726

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000157

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1250A>G (p.N417S) alteration is located in exon 11 (coding exon 11) of the DDX19B gene. This alteration results from a A to G substitution at nucleotide position 1250, causing the asparagine (N) at amino acid position 417 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

0.13

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.19

.;T;.;.;T;.;.

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.042

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.88

.;D;D;.;D;D;D

M_CAP

Benign

0.031

MetaRNN

Benign

0.095

T;T;T;T;T;T;T

MetaSVM

Benign

-0.67

MutationAssessor

Benign

-0.47

.;.;.;.;N;.;.

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.78

N;N;N;N;N;N;N

REVEL

Benign

0.097

Sift

Benign

0.20

T;T;T;T;T;T;T

Sift4G

Benign

0.37

T;T;T;T;T;T;T

Polyphen

0.0070, 0.57

.;.;.;.;B;.;P

Vest4

0.37

MutPred

0.35

.;.;.;.;Gain of phosphorylation at N417 (P = 0.0571);.;.;

MVP

0.18

MPC

1.3

ClinPred

0.090

GERP RS

4.0

Varity_R

0.18

gMVP

0.75

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