Variant 16-70370337-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_018332.5(DDX19A):c.1135C>G(p.Arg379Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,758 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: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

DDX19A
NM_018332.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.424

Variant links:

Genes affected

DDX19A (HGNC:25628): (DEAD-box helicase 19A) Predicted to enable RNA binding activity and RNA helicase activity. Predicted to be involved in poly(A)+ mRNA export from nucleus. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

DDX19A links:

ENSG00000260537 (HGNC:):

ENSG00000260537 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.975

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX19A	NM_018332.5 linkuse as main transcript	c.1135C>G	p.Arg379Gly	missense_variant	10/12	ENST00000302243.12	NP_060802.1	Q9NUU7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX19A	ENST00000302243.12 linkuse as main transcript	c.1135C>G	p.Arg379Gly	missense_variant	10/12	1	NM_018332.5	ENSP00000306117.7		Q9NUU7-1
ENSG00000260537	ENST00000443119.7 linkuse as main transcript	c.1138C>G	p.Arg380Gly	missense_variant	10/12	5		ENSP00000399208.3		F6QDS0

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152032

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:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

251340

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461726

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727162

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:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152032

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74236

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:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Jan 06, 2023

The c.1135C>G (p.R379G) alteration is located in exon 10 (coding exon 10) of the DDX19A gene. This alteration results from a C to G substitution at nucleotide position 1135, causing the arginine (R) at amino acid position 379 to be replaced by a glycine (G). 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

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Pathogenic

0.28

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.68

.;D;.

Eigen

Uncertain

0.36

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.89

LIST_S2

Pathogenic

0.99

D;D;D

M_CAP

Uncertain

0.26

MetaRNN

Pathogenic

0.97

D;D;D

MetaSVM

Uncertain

0.086

MutationAssessor

Uncertain

2.9

.;M;.

PROVEAN

Pathogenic

-6.6

.;D;D

REVEL

Pathogenic

0.72

Sift

Pathogenic

0.0

.;D;D

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

1.0

.;D;.

Vest4

0.92

MutPred

0.88

.;Loss of MoRF binding (P = 0.0499);.;

MVP

0.97

MPC

1.4

ClinPred

0.97

GERP RS

-1.1

Varity_R

0.93

gMVP

0.99

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