chr16-70347031-G-A

Position:

• chr16-70347031-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018332.5(DDX19A):​c.40G>A​(p.Glu14Lys) 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: 33)
• Consequence: DDX19A NM_018332.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.75

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29451063).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX19A	NM_018332.5	c.40G>A	p.Glu14Lys	missense_variant	1/12	ENST00000302243.12	NP_060802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX19A	ENST00000302243.12	c.40G>A	p.Glu14Lys	missense_variant	1/12	1	NM_018332.5	ENSP00000306117.7
ENSG00000260537	ENST00000443119.7	c.161-9081G>A		intron_variant		5		ENSP00000399208.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 13, 2022

The c.40G>A (p.E14K) alteration is located in exon 1 (coding exon 1) of the DDX19A gene. This alteration results from a G to A substitution at nucleotide position 40, causing the glutamic acid (E) at amino acid position 14 to be replaced by a lysine (K). 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	0.94
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.087	T;.
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.2	M;.
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.14
Sift	Uncertain	0.0040	D;D
Sift4G	Benign	0.29	T;T
Polyphen		0.23	B;.
Vest4		0.65
MutPred		0.34		Gain of ubiquitination at E14 (P = 0.0114);Gain of ubiquitination at E14 (P = 0.0114);
MVP		0.72
MPC		1.6
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.59
gMVP		0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-70380934;