16-70355506-C-T

Variant names:

• chr16-70355506-C-T
• rs771388403
• NM_018332.5:c.128C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001320525.2(DDX19A):​c.-204C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,613,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: DDX19A NM_001320525.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.56
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.036790043).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320525.2. 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.128C>T	p.Thr43Ile	missense	Exon 3 of 12	NP_060802.1	Q9NUU7-1
	DDX19A	NM_001320525.2		c.-204C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 13	NP_001307454.1	Q9NUU7-2
	DDX19A	NM_001320526.2		c.-449C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 12	NP_001307455.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX19A	ENST00000302243.12	TSL:1 MANE Select	c.128C>T	p.Thr43Ile	missense	Exon 3 of 12	ENSP00000306117.7	Q9NUU7-1
	ENSG00000260537	ENST00000443119.7	TSL:5	c.161-606C>T		intron	N/A	ENSP00000399208.3	F6QDS0
	DDX19A	ENST00000569319.5	TSL:1	n.128C>T		non_coding_transcript_exon	Exon 3 of 11	ENSP00000456765.1	H3BSL8

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152178 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000756 AC: 19 AN: 251422 AF XY: 0.0000442

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000549

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.0000130 AC: 19 AN: 1461674 Hom.: 0 Cov.: 29 AF XY: 0.00000963 AC XY: 7 AN XY: 727152

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000425 AC: 19 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111814

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152178 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74332

African (AFR) AF: 0.00 AC: 0 AN: 41432

American (AMR) AF: 0.000131 AC: 2 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000741 AC: 9

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	Benign	0.079
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.068	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.49	N
PhyloP100		2.6
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.048
Sift	Benign	0.088	T
Sift4G	Benign	0.093	T
Polyphen		0.0	B
Vest4		0.20
MutPred		0.12		Loss of phosphorylation at T43 (P = 0.0137)
MVP		0.24
MPC		0.65
ClinPred		0.049	T
GERP RS		2.8
Varity_R		0.041
gMVP		0.45

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

Other links and lift over

dbSNP: rs771388403; hg19: chr16-70389409;