rs311686

Positions:

• chr6-73416152-A-C
• chr6-73416152-A-G
• chr6-73416152-A-T

Variant summary

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

The ENST00000370336.5(DDX43):​c.1873A>C​(p.Lys625Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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. K625E) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DDX43 ENST00000370336.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.59

Genes affected

DDX43 (HGNC:18677): (DEAD-box helicase 43) The protein encoded by this gene is an ATP-dependent RNA helicase in the DEAD-box family and displays tumor-specific expression. [provided by RefSeq, Jul 2008]

CGAS (HGNC:21367): (cyclic GMP-AMP synthase) Enables several functions, including 2',3'-cyclic GMP-AMP synthase activity; chromatin binding activity; and phosphatidylinositol-4,5-bisphosphate binding activity. Involved in several processes, including cellular response to exogenous dsRNA; positive regulation of intracellular signal transduction; and regulation of defense response. Located in several cellular components, including cytosol; nucleus; and site of double-strand break. [provided by Alliance of Genome Resources, Apr 2022]

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=0.076060474).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX43	NM_018665.3	c.1873A>C	p.Lys625Gln	missense_variant	16/17	ENST00000370336.5	NP_061135.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX43	ENST00000370336.5	c.1873A>C	p.Lys625Gln	missense_variant	16/17	1	NM_018665.3	ENSP00000359361	P1
CGAS	ENST00000370318.5	c.1333-2131T>G		intron_variant		1		ENSP00000359342

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	13
DANN	Benign	0.72
DEOGEN2	Benign	0.0068	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.38
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
MutationTaster	Benign	0.54	P;P
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.078
Sift	Benign	0.090	T
Sift4G	Benign	0.18	T
Polyphen		0.049	B
Vest4		0.057
MutPred		0.23		Loss of methylation at K625 (P = 0.0019);
MVP		0.37
MPC		0.38
ClinPred		0.31	T
GERP RS		4.1
Varity_R		0.078
gMVP		0.50

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

LitVar

Other links and lift over

dbSNP: rs311686; hg19: chr6-74125875;