NM_018332.5:c.370A>C

Variant names:

• chr16-70361494-A-C
• rs1453668783
• NM_018332.5:c.370A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018332.5(DDX19A):​c.370A>C​(p.Met124Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000959 in 1,459,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M124V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: DDX19A NM_018332.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.93
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08365902).

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.370A>C	p.Met124Leu	missense	Exon 5 of 12	NP_060802.1	Q9NUU7-1
	DDX19A	NM_001320526.2		c.-207A>C		5_prime_UTR_premature_start_codon_gain	Exon 5 of 12	NP_001307455.1
	DDX19A	NM_001320527.2		c.-314A>C		5_prime_UTR_premature_start_codon_gain	Exon 4 of 11	NP_001307456.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX19A	ENST00000302243.12	TSL:1 MANE Select	c.370A>C	p.Met124Leu	missense	Exon 5 of 12	ENSP00000306117.7	Q9NUU7-1
	ENSG00000260537	ENST00000443119.7	TSL:5	c.373A>C	p.Met125Leu	missense	Exon 5 of 12	ENSP00000399208.3	F6QDS0
	DDX19A	ENST00000569319.5	TSL:1	n.234A>C		non_coding_transcript_exon	Exon 4 of 11	ENSP00000456765.1	H3BSL8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000959 AC: 14 AN: 1459792 Hom.: 0 Cov.: 29 AF XY: 0.00000826 AC XY: 6 AN XY: 726388

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53162

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1110422

Other (OTH) AF: 0.00 AC: 0 AN: 60340

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	19
DANN	Benign	0.72
DEOGEN2	Benign	0.044	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.62
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.7	N
PhyloP100		6.9
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.21
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.44
MutPred		0.45		Loss of disorder (P = 0.0797)
MVP		0.22
MPC		0.72
ClinPred		0.20	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.48
Mutation Taster		=58/42	polymorphism

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: rs1453668783; hg19: chr16-70395397;