NM_018332.5:c.1126G>A

Variant names:

• chr16-70370328-G-A
• NM_018332.5:c.1126G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018332.5(DDX19A):​c.1126G>A​(p.Glu376Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: DDX19A NM_018332.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.22
• Publications: 0 publications found

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]

ENSG00000260537 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3556065).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018332.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX19A	NM_018332.5	MANE Select	c.1126G>A	p.Glu376Lys	missense	Exon 10 of 12	NP_060802.1	Q9NUU7-1
	DDX19A	NM_001320522.2		c.1033G>A	p.Glu345Lys	missense	Exon 9 of 11	NP_001307451.1	I3L0H8
	DDX19A	NM_001320525.2		c.856G>A	p.Glu286Lys	missense	Exon 11 of 13	NP_001307454.1	Q9NUU7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX19A	ENST00000302243.12	TSL:1 MANE Select	c.1126G>A	p.Glu376Lys	missense	Exon 10 of 12	ENSP00000306117.7	Q9NUU7-1
	ENSG00000260537	ENST00000443119.7	TSL:5	c.1129G>A	p.Glu377Lys	missense	Exon 10 of 12	ENSP00000399208.3	F6QDS0
	DDX19A	ENST00000566574.5	TSL:1	n.3306G>A		non_coding_transcript_exon	Exon 3 of 5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.17
Eigen_PC	Benign	0.075
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	0.14	N
PhyloP100		6.2
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.30
Sift	Benign	0.14	T
Sift4G	Benign	0.16	T
Polyphen		0.86	P
Vest4		0.41
MutPred		0.47		Gain of MoRF binding (P = 9e-04)
MVP		0.64
MPC		0.94
ClinPred		0.90	D
GERP RS		5.2
Varity_R		0.36
gMVP		0.88

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

Other links and lift over

hg19: chr16-70404231;