9-132630303-T-C

Position:

• chr9-132630303-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

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]

DDX31 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX31	NM_022779.9	c.1592A>G	p.Glu531Gly	missense_variant	16/20	ENST00000372159.8	NP_073616.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX31	ENST00000372159.8	c.1592A>G	p.Glu531Gly	missense_variant	16/20	1	NM_022779.9	ENSP00000361232.4

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

Gnomad4 AFR exome AF: 0.0000602

Gnomad4 AMR exome AF: 0.00

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.: 33

Bravo AF: 0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 30, 2024

The c.1907A>G (p.E636G) alteration is located in exon 16 (coding exon 16) of the DDX31 gene. This alteration results from a A to G substitution at nucleotide position 1907, causing the glutamic acid (E) at amino acid position 636 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;.
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.90	.;D;D
M_CAP	Benign	0.032	D
MetaRNN	Pathogenic	0.86	D;D;D
MetaSVM	Benign	-0.91	T
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-6.7	D;.;.
REVEL	Uncertain	0.39
Sift	Uncertain	0.0040	D;.;.
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.96
MutPred		0.62		Gain of glycosylation at S635 (P = 0.052);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

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

LitVar

Other links and lift over

dbSNP: rs766931553; hg19: chr9-135505690;