rs368425075

Variant names:

• chr6-73406404-T-C
• rs368425075
• NM_018665.3:c.848T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_018665.3(DDX43):​c.848T>C​(p.Ile283Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000108 in 1,613,394 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: DDX43 NM_018665.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.12
• Publications: 0 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.858

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.848T>C	p.Ile283Thr	missense	Exon 7 of 17	NP_061135.2	Q9NXZ2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX43	ENST00000370336.5	TSL:1 MANE Select	c.848T>C	p.Ile283Thr	missense	Exon 7 of 17	ENSP00000359361.4	Q9NXZ2-1
	DDX43	ENST00000942801.1		c.848T>C	p.Ile283Thr	missense	Exon 7 of 16	ENSP00000612860.1
	DDX43	ENST00000901441.1		c.716T>C	p.Ile239Thr	missense	Exon 6 of 16	ENSP00000571500.1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000677 AC: 17 AN: 251242 AF XY: 0.0000884

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000141

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000114 AC: 166 AN: 1461178 Hom.: 0 Cov.: 29 AF XY: 0.000114 AC XY: 83 AN XY: 726928

African (AFR) AF: 0.0000299 AC: 1 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.000144 AC: 160 AN: 1111492

Other (OTH) AF: 0.0000828 AC: 5 AN: 60368

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152216 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74366

African (AFR) AF: 0.0000241 AC: 1 AN: 41450

American (AMR) AF: 0.0000655 AC: 1 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000165 Hom.: 0

Bravo AF: 0.0000529

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000824 AC: 10

EpiCase AF: 0.000218

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.089	T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.060	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Benign	-0.94	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		7.1
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Uncertain	0.57
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.95
MVP		0.68
MPC		1.2
ClinPred		0.90	D
GERP RS		5.1
Varity_R		0.74
gMVP		0.59
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs368425075; hg19: chr6-74116127;