16-70333562-ATT-CTC

Variant names:

• chr16-70333562-ATT-CTC
• NM_007242.7:c.1420_1422delATTinsCTC
• DDX19B p.Ile474Leu

Variant summary

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

The NM_007242.7(DDX19B):​c.1420_1422delATTinsCTC​(p.Ile474Leu) 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. I474V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DDX19B NM_007242.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.38
• Publications: 0 publications found

Genes affected

DDX19B (HGNC:2742): (DEAD-box helicase 19B) DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which exhibits RNA-dependent ATPase and ATP-dependent RNA-unwinding activities. This protein is recruited to the cytoplasmic fibrils of the nuclear pore complex, where it participates in the export of mRNA from the nucleus. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ENSG00000260537 (HGNC:):

DDX19A-DT (HGNC:55349): (DDX19A divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007242.7. 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
	DDX19B	NM_007242.7	MANE Select	c.1420_1422delATTinsCTC	p.Ile474Leu	missense	N/A	NP_009173.1	Q9UMR2-1
	DDX19B	NM_001363938.1		c.1435_1437delATTinsCTC	p.Ile479Leu	missense	N/A	NP_001350867.1	H3BQK0
	DDX19B	NM_001257172.2		c.1342_1344delATTinsCTC	p.Ile448Leu	missense	N/A	NP_001244101.1	Q9UMR2-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX19B	ENST00000288071.11	TSL:1 MANE Select	c.1420_1422delATTinsCTC	p.Ile474Leu	missense	N/A	ENSP00000288071.7	Q9UMR2-1
	DDX19B	ENST00000355992.7	TSL:1	c.1327_1329delATTinsCTC	p.Ile443Leu	missense	N/A	ENSP00000348271.3	Q9UMR2-2
	DDX19B	ENST00000393657.6	TSL:1	c.1093_1095delATTinsCTC	p.Ile365Leu	missense	N/A	ENSP00000377267.2	Q9UMR2-3

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.4

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: chr16-70367465;