NM_004397.6:c.1175-7_1175-4delTTTT

Variant names:

• chr11-118755506-TAAAA-T
• rs551201488
• NM_004397.6:c.1175-7_1175-4delTTTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004397.6(DDX6):​c.1175-7_1175-4delTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000915 in 1,092,834 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.2e-7 (0 hom.)
• Consequence: DDX6 NM_004397.6 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.36

Genes affected

DDX6 (HGNC:2747): (DEAD-box helicase 6) This gene encodes a member of the DEAD box protein family. The protein is an RNA helicase found in P-bodies and stress granules, and functions in translation suppression and mRNA degradation. It is required for microRNA-induced gene silencing. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Mar 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX6	NM_004397.6	c.1175-7_1175-4delTTTT		splice_region_variant, intron_variant	Intron 11 of 13	ENST00000534980.7	NP_004388.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX6	ENST00000534980.7	c.1175-7_1175-4delTTTT		splice_region_variant, intron_variant	Intron 11 of 13	1	NM_004397.6	ENSP00000442266.1
DDX6	ENST00000526070.2	c.1175-7_1175-4delTTTT		splice_region_variant, intron_variant	Intron 11 of 12	1		ENSP00000433704.1
DDX6	ENST00000620157.4	c.1175-7_1175-4delTTTT		splice_region_variant, intron_variant	Intron 11 of 13	1		ENSP00000478754.1
DDX6	ENST00000529162.1	n.778-7_778-4delTTTT		splice_region_variant, intron_variant	Intron 3 of 5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000788 AC: 1 AN: 126892 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 68378

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000721

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS 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: 9.15e-7 AC: 1 AN: 1092834 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 546832

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000310

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs551201488; hg19: chr11-118626215;