chr6-73394922-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018665.3(DDX43):​c.17G>A​(p.Gly6Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00291 in 1,614,190 control chromosomes in the GnomAD database, including 110 homozygotes. 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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (56 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (54 hom.)
• Consequence: DDX43 NM_018665.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0021864772).
• BP6: Variant 6-73394922-G-A is Benign according to our data. Variant chr6-73394922-G-A is described in ClinVar as Benign. ClinVar VariationId is 776131.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0526 is higher than 0.05.

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>A	p.Gly6Glu	missense	Exon 1 of 17	NP_061135.2	Q9NXZ2-1
	OOEP	NM_001428256.1		c.-552C>T		5_prime_UTR	Exon 1 of 3	NP_001415185.1	F2Z364
	OOEP	NR_190285.1		n.242C>T		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>A	p.Gly6Glu	missense	Exon 1 of 17	ENSP00000359361.4	Q9NXZ2-1
	OOEP	ENST00000370363.5	TSL:1	c.-322C>T		5_prime_UTR	Exon 1 of 4	ENSP00000359388.1	F2Z364
	DDX43	ENST00000942801.1		c.17G>A	p.Gly6Glu	missense	Exon 1 of 16	ENSP00000612860.1

Frequencies

GnomAD3 genomes AF: 0.0155 AC: 2354 AN: 152208 Hom.: 55 Cov.: 32

Gnomad AFR AF: 0.0541

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00530

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.00408 AC: 1024 AN: 251142 AF XY: 0.00308

Gnomad AFR exome AF: 0.0558

Gnomad AMR exome AF: 0.00295

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00159 AC: 2318 AN: 1461864 Hom.: 54 Cov.: 34 AF XY: 0.00138 AC XY: 1003 AN XY: 727228

African (AFR) AF: 0.0559 AC: 1873 AN: 33480

American (AMR) AF: 0.00371 AC: 166 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00225 AC: 13 AN: 5766

European-Non Finnish (NFE) AF: 0.0000234 AC: 26 AN: 1112002

Other (OTH) AF: 0.00387 AC: 234 AN: 60396

GnomAD4 genome AF: 0.0156 AC: 2377 AN: 152326 Hom.: 56 Cov.: 32 AF XY: 0.0149 AC XY: 1113 AN XY: 74488

African (AFR) AF: 0.0545 AC: 2265 AN: 41570

American (AMR) AF: 0.00529 AC: 81 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68024

Other (OTH) AF: 0.0113 AC: 24 AN: 2116

Alfa AF: 0.00598 Hom.: 33

Bravo AF: 0.0173

ESP6500AA AF: 0.0470 AC: 207

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00488 AC: 592

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.2
DANN	Benign	0.80
DEOGEN2	Benign	0.00041	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.31	T
MetaRNN	Benign	0.0022	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N
PhyloP100		-0.35
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.26	N
REVEL	Benign	0.016
Sift	Benign	0.61	T
Sift4G	Benign	0.64	T
Polyphen		0.0	B
Vest4		0.064
MVP		0.13
MPC		0.43
ClinPred		0.0020	T
GERP RS		0.016
PromoterAI		-0.0028	Neutral
Varity_R		0.035
gMVP		0.19
Mutation Taster		=300/0	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;