X-23000545-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_182699.4(DDX53):c.488G>A(p.Cys163Tyr) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: DDX53 NM_182699.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.51

Genes affected

DDX53 (HGNC:20083): (DEAD-box helicase 53) This intronless gene encodes a protein which contains several domains found in members of the DEAD-box helicase protein family. Other members of this protein family participate in ATP-dependent RNA unwinding. [provided by RefSeq, Sep 2011]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.041367143).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX53	NM_182699.4	c.488G>A	p.Cys163Tyr	missense_variant	1/1	ENST00000327968.7
PTCHD1-AS	NR_073010.2	n.343+63493C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX53	ENST00000327968.7	c.488G>A	p.Cys163Tyr	missense_variant	1/1		NM_182699.4	P1
	ENST00000687248.1	n.343+63493C>T		intron_variant, non_coding_transcript_variant
	ENST00000687119.1	n.83-56397C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Oct 21, 2016

The C163Y variant in the DDX53 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The C163Y variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The C163Y variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is not conserved. In silico analysis predicts this variant likely does not alter the protein structure/function. We interpret C163Y as a variant of uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.97
Cadd	Benign	2.9
Dann	Benign	0.43
DEOGEN2	Benign	0.0033	T
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.4	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	4.7	N
REVEL	Benign	0.13
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.23
MutPred		0.40		Gain of phosphorylation at C163 (P = 0.0501);
MVP		0.043
MPC		0.15
ClinPred		0.042	T
GERP RS		3.9
Varity_R		0.049
gMVP		0.37

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

LitVar

Other links and lift over

dbSNP: rs1064795781; hg19: chrX-23018662;