19-18922408-CG-TC

Variant names:

• chr19-18922408-CG-TC
• NM_019070.5:c.530_531delCGinsTC
• DDX49 p.Pro177Leu

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_019070.5(DDX49):​c.530_531delCGinsTC​(p.Pro177Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. P177R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DDX49 NM_019070.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.56
• Publications: 0 publications found

Genes affected

DDX49 (HGNC:18684): (DEAD-box helicase 49) Enables RNA binding activity. Involved in positive regulation of cell growth and regulation of rRNA stability. Predicted to be located in nucleoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000268193 (HGNC:):

ACMG classification

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

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019070.5. 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
	DDX49	NM_019070.5	MANE Select	c.530_531delCGinsTC	p.Pro177Leu	missense	N/A	NP_061943.2
	DDX49	NR_033677.2		n.486_487delCGinsTC		non_coding_transcript_exon	Exon 5 of 13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX49	ENST00000247003.9	TSL:1 MANE Select	c.530_531delCGinsTC	p.Pro177Leu	missense	N/A	ENSP00000247003.3	Q9Y6V7-1
	DDX49	ENST00000595858.5	TSL:1	n.*105_*106delCGinsTC		non_coding_transcript_exon	Exon 6 of 14	ENSP00000471292.1	M0R0K1
	DDX49	ENST00000602113.5	TSL:1	n.*333_*334delCGinsTC		non_coding_transcript_exon	Exon 5 of 13	ENSP00000469086.1	M0QXD4

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-19033217;