9-132594981-C-G

Variant names:

• chr9-132594981-C-G
• NM_022779.9:c.2126G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022779.9(DDX31):​c.2126G>C​(p.Arg709Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: DDX31 NM_022779.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.274

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08020052).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX31	NM_022779.9	c.2126G>C	p.Arg709Pro	missense_variant	Exon 20 of 20	ENST00000372159.8	NP_073616.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX31	ENST00000372159.8	c.2126G>C	p.Arg709Pro	missense_variant	Exon 20 of 20	1	NM_022779.9	ENSP00000361232.4
DDX31	ENST00000372155.2	n.359G>C		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461876 Hom.: 0 Cov.: 36 AF XY: 0.00000688 AC XY: 5 AN XY: 727238

Gnomad4 AFR exome AF: 0.00

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: 0.00000360

Gnomad4 OTH exome AF: 0.0000497

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2441G>C (p.R814P) alteration is located in exon 20 (coding exon 20) of the DDX31 gene. This alteration results from a G to C substitution at nucleotide position 2441, causing the arginine (R) at amino acid position 814 to be replaced by a proline (P). 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	Benign	0.10
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.18
DANN	Benign	0.72
DEOGEN2	Benign	0.0013	T;T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.51	.;T;T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.080	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.34	N;N;.
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.88	N;.;.
REVEL	Benign	0.026
Sift	Uncertain	0.014	D;.;.
Sift4G	Benign	0.29	T;T;T
Polyphen		0.0020	B;B;.
Vest4		0.10
MutPred		0.29		Gain of glycosylation at R814 (P = 0.0093);Gain of glycosylation at R814 (P = 0.0093);.;
MVP		0.22
MPC		0.22
ClinPred		0.37	T
GERP RS		-1.2
Varity_R		0.14
gMVP		0.060

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr9-135470368;