9-132630303-T-C

Variant names:

• chr9-132630303-T-C
• rs766931553
• NM_022779.9:c.1592A>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_022779.9(DDX31):​c.1592A>G​(p.Glu531Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000139 in 1,441,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DDX31 NM_022779.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.25
• Publications: 0 publications found

Genes affected

DDX31 (HGNC:16715): (DEAD-box helicase 31) 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 DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a member of this family. The function of this member has not been determined. Alternative splicing of this gene generates multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.864

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022779.9. 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
	DDX31	NM_022779.9	MANE Select	c.1592A>G	p.Glu531Gly	missense	Exon 16 of 20	NP_073616.7
	DDX31	NM_001322341.2		c.1619A>G	p.Glu540Gly	missense	Exon 17 of 21	NP_001309270.1
	DDX31	NM_001322343.1		c.1520A>G	p.Glu507Gly	missense	Exon 16 of 20	NP_001309272.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX31	ENST00000372159.8	TSL:1 MANE Select	c.1592A>G	p.Glu531Gly	missense	Exon 16 of 20	ENSP00000361232.4	Q9H8H2-5
	DDX31	ENST00000893393.1		c.1736A>G	p.Glu579Gly	missense	Exon 17 of 21	ENSP00000563452.1
	DDX31	ENST00000893392.1		c.1592A>G	p.Glu531Gly	missense	Exon 16 of 20	ENSP00000563451.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1441824 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 712970

African (AFR) AF: 0.0000602 AC: 2 AN: 33198

American (AMR) AF: 0.00 AC: 0 AN: 44320

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25944

East Asian (EAS) AF: 0.00 AC: 0 AN: 39114

South Asian (SAS) AF: 0.00 AC: 0 AN: 85166

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53212

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1095710

Other (OTH) AF: 0.00 AC: 0 AN: 59456

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.26	T
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.032	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Benign	-0.91	T
PhyloP100		6.3
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-6.7	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0040	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.96
MutPred		0.62		Gain of glycosylation at S635 (P = 0.052)
MVP		0.66
MPC		0.71
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.64
gMVP		0.75
Mutation Taster		=16/84	disease causing

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

Other links and lift over

dbSNP: rs766931553; hg19: chr9-135505690;