chr6-73395048-G-C

Position:

• chr6-73395048-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018665.3(DDX43):​c.143G>C​(p.Gly48Ala) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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: 0.341

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]

DDX43 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13446459).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX43	NM_018665.3	c.143G>C	p.Gly48Ala	missense_variant	1/17	ENST00000370336.5	NP_061135.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX43	ENST00000370336.5	c.143G>C	p.Gly48Ala	missense_variant	1/17	1	NM_018665.3	ENSP00000359361.4
OOEP	ENST00000370363.5	c.-448C>G		5_prime_UTR_variant	1/4	1		ENSP00000359388.1
OOEP	ENST00000441145.1	c.-678C>G		5_prime_UTR_variant	1/2	3		ENSP00000397430.1
DDX43	ENST00000464221.1	n.155G>C		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 31, 2023

The c.143G>C (p.G48A) alteration is located in exon 1 (coding exon 1) of the DDX43 gene. This alteration results from a G to C substitution at nucleotide position 143, causing the glycine (G) at amino acid position 48 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	11
DANN	Benign	0.87
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.095	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.021
Sift	Benign	0.073	T
Sift4G	Benign	0.10	T
Polyphen		0.84	P
Vest4		0.20
MutPred		0.19		Gain of sheet (P = 0.0166);
MVP		0.36
MPC		0.36
ClinPred		0.18	T
GERP RS		2.0
Varity_R		0.082
gMVP		0.22

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-74104771;