NM_018665.3:c.956T>C

Variant names:

• chr6-73407534-T-C
• NM_018665.3:c.956T>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_018665.3(DDX43):​c.956T>C​(p.Met319Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M319I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DDX43 NM_018665.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.84
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.843

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.956T>C	p.Met319Thr	missense	Exon 8 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.956T>C	p.Met319Thr	missense	Exon 8 of 17	ENSP00000359361.4	Q9NXZ2-1
	DDX43	ENST00000942801.1		c.956T>C	p.Met319Thr	missense	Exon 8 of 16	ENSP00000612860.1
	DDX43	ENST00000901441.1		c.824T>C	p.Met275Thr	missense	Exon 7 of 16	ENSP00000571500.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

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	Pathogenic	0.75
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.028	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.46	N
PhyloP100		6.8
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.031	D
Polyphen		0.99	D
Vest4		0.90
MutPred		0.52		Gain of phosphorylation at M319 (P = 0.0288)
MVP		0.57
MPC		1.0
ClinPred		0.98	D
GERP RS		4.9
Varity_R		0.54
gMVP		0.51
Mutation Taster		=65/35	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

hg19: chr6-74117257;