NM_018665.3:c.17G>T

Variant names:

• chr6-73394922-G-T
• rs35097680
• NM_018665.3:c.17G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018665.3(DDX43):​c.17G>T​(p.Gly6Val) 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DDX43 NM_018665.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.352

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]

OOEP (HGNC:21382): (oocyte expressed protein) Predicted to enable RNA binding activity. Predicted to be involved in several processes, including cytoskeleton organization; positive regulation of double-strand break repair via homologous recombination; and positive regulation of meiotic nuclear division. Predicted to act upstream of or within several processes, including embryo implantation; in utero embryonic development; and protein phosphorylation. Located in cytoplasm and nucleus. Part of subcortical maternal complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.063321054).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX43	NM_018665.3	c.17G>T	p.Gly6Val	missense_variant	Exon 1 of 17	ENST00000370336.5	NP_061135.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX43	ENST00000370336.5	c.17G>T	p.Gly6Val	missense_variant	Exon 1 of 17	1	NM_018665.3	ENSP00000359361.4
OOEP	ENST00000370363.5	c.-322C>A		5_prime_UTR_variant	Exon 1 of 4	1		ENSP00000359388.1
OOEP	ENST00000441145.1	c.-552C>A		5_prime_UTR_variant	Exon 1 of 2	3		ENSP00000397430.1
DDX43	ENST00000464221.1	n.29G>T		non_coding_transcript_exon_variant	Exon 1 of 2	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.9
DANN	Benign	0.82
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.017
Sift	Benign	0.17	T
Sift4G	Benign	0.15	T
Polyphen		0.012	B
Vest4		0.16
MutPred		0.14		Loss of relative solvent accessibility (P = 0.0186);
MVP		0.19
MPC		0.43
ClinPred		0.045	T
GERP RS		0.016
Varity_R		0.044
gMVP		0.23

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: rs35097680; hg19: chr6-74104645;