6-73394922-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. 16/22 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. G6E) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DDX43 NM_018665.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.352
• Publications: 2 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018665.3. 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
	DDX43	NM_018665.3	MANE Select	c.17G>T	p.Gly6Val	missense	Exon 1 of 17	NP_061135.2	Q9NXZ2-1
	OOEP	NM_001428256.1		c.-552C>A		5_prime_UTR	Exon 1 of 3	NP_001415185.1	F2Z364
	OOEP	NR_190285.1		n.242C>A		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX43	ENST00000370336.5	TSL:1 MANE Select	c.17G>T	p.Gly6Val	missense	Exon 1 of 17	ENSP00000359361.4	Q9NXZ2-1
	OOEP	ENST00000370363.5	TSL:1	c.-322C>A		5_prime_UTR	Exon 1 of 4	ENSP00000359388.1	F2Z364
	DDX43	ENST00000942801.1		c.17G>T	p.Gly6Val	missense	Exon 1 of 16	ENSP00000612860.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		-0.35
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
PromoterAI		0.023	Neutral
Varity_R		0.044
gMVP		0.23
Mutation Taster		=98/2	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: rs35097680; hg19: chr6-74104645;