11-118754879-C-T

Variant names:

• chr11-118754879-C-T
• NM_004397.6:c.1285G>A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_004397.6(DDX6):​c.1285G>A​(p.Gly429Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DDX6 NM_004397.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.968

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX6	NM_004397.6	c.1285G>A	p.Gly429Ser	missense_variant	Exon 13 of 14	ENST00000534980.7	NP_004388.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX6	ENST00000534980.7	c.1285G>A	p.Gly429Ser	missense_variant	Exon 13 of 14	1	NM_004397.6	ENSP00000442266.1
DDX6	ENST00000526070.2	c.1285G>A	p.Gly429Ser	missense_variant	Exon 13 of 13	1		ENSP00000433704.1
DDX6	ENST00000620157.4	c.1285G>A	p.Gly429Ser	missense_variant	Exon 13 of 14	1		ENSP00000478754.1
DDX6	ENST00000529162.1	n.888G>A		non_coding_transcript_exon_variant	Exon 5 of 6	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Jul 08, 2022

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.70	D;D;D
Eigen	Pathogenic	0.94
Eigen_PC	Pathogenic	0.91
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.99	D;.;.
M_CAP	Benign	0.052	D
MetaRNN	Pathogenic	0.97	D;D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Pathogenic	3.0	M;M;M
PrimateAI	Pathogenic	0.89	D
PROVEAN	Pathogenic	-5.9	.;D;D
REVEL	Uncertain	0.58
Sift	Pathogenic	0.0	.;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.77
MutPred		0.92		Loss of catalytic residue at G429 (P = 0.0625);Loss of catalytic residue at G429 (P = 0.0625);Loss of catalytic residue at G429 (P = 0.0625);
MVP		0.69
ClinPred		1.0	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.92
gMVP		0.96

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-118625588;