5-134794857-GC-TA

Variant names:

• chr5-134794857-GC-TA
• NM_001300860.2:c.1634_1635delGCinsTA
• DDX46 p.Arg545Leu

Variant summary

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

The NM_001300860.2(DDX46):​c.1634_1635delGCinsTA​(p.Arg545Leu) 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. R545H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DDX46 NM_001300860.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.84
• Publications: 0 publications found

Genes affected

DDX46 (HGNC:18681): (DEAD-box helicase 46) This gene encodes a member of the DEAD box protein family. 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. The protein encoded by this gene is a component of the 17S U2 snRNP complex; it plays an important role in pre-mRNA splicing. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2014]

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_001300860.2. 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
	DDX46	NM_001300860.2	MANE Select	c.1634_1635delGCinsTA	p.Arg545Leu	missense	N/A	NP_001287789.1	A0A0C4DG89
	DDX46	NM_014829.4		c.1634_1635delGCinsTA	p.Arg545Leu	missense	N/A	NP_055644.2
	DDX46	NR_125341.2		n.1767_1768delGCinsTA		non_coding_transcript_exon	Exon 14 of 23

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX46	ENST00000452510.7	TSL:1 MANE Select	c.1634_1635delGCinsTA	p.Arg545Leu	missense	N/A	ENSP00000416534.2	A0A0C4DG89
	DDX46	ENST00000354283.8	TSL:1	c.1634_1635delGCinsTA	p.Arg545Leu	missense	N/A	ENSP00000346236.4	Q7L014
	DDX46	ENST00000507392.5	TSL:2	n.*191_*192delGCinsTA		non_coding_transcript_exon	Exon 14 of 23	ENSP00000427290.1	D6RJA6

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		9.8

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: chr5-134130547;