NM_022779.9:c.1795A>C

Variant names:

• chr9-132618360-T-G
• rs199750353
• NM_022779.9:c.1795A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_022779.9(DDX31):​c.1795A>C​(p.Ser599Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 1,459,096 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S599G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: DDX31 NM_022779.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.784
• Publications: 2 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 2 ACMG points.

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

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.1795A>C	p.Ser599Arg	missense	Exon 18 of 20	NP_073616.7
	DDX31	NM_001322341.2		c.1822A>C	p.Ser608Arg	missense	Exon 19 of 21	NP_001309270.1
	DDX31	NM_001322343.1		c.1723A>C	p.Ser575Arg	missense	Exon 18 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.1795A>C	p.Ser599Arg	missense	Exon 18 of 20	ENSP00000361232.4	Q9H8H2-5
	DDX31	ENST00000893393.1		c.1939A>C	p.Ser647Arg	missense	Exon 19 of 21	ENSP00000563452.1
	DDX31	ENST00000893392.1		c.1771A>C	p.Ser591Arg	missense	Exon 18 of 20	ENSP00000563451.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000117 AC: 17 AN: 1459096 Hom.: 0 Cov.: 30 AF XY: 0.00000551 AC XY: 4 AN XY: 725726

African (AFR) AF: 0.00 AC: 0 AN: 33430

American (AMR) AF: 0.00 AC: 0 AN: 44166

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39578

South Asian (SAS) AF: 0.00 AC: 0 AN: 85372

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1110950

Other (OTH) AF: 0.00 AC: 0 AN: 60310

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0061	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.041
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		0.78
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.18
Sift	Benign	0.062	T
Sift4G	Benign	0.33	T
Polyphen		0.95	P
Vest4		0.58
MutPred		0.42		Loss of phosphorylation at S704 (P = 0.0384)
MVP		0.52
MPC		0.54
ClinPred		0.73	D
GERP RS		3.4
Varity_R		0.090
gMVP		0.51
Mutation Taster		=82/18	polymorphism

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

Other links and lift over

dbSNP: rs199750353; hg19: chr9-135493747;