X-23000480-T-A

Position:

• chrX-23000480-T-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.423T>A​(p.Asn141Lys) 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: 23)
• Consequence: DDX53 NM_182699.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.270

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]

ENSG00000289084 (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=0.06010413).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX53	NM_182699.4	c.423T>A	p.Asn141Lys	missense_variant	1/1	ENST00000327968.7	NP_874358.2
PTCHD1-AS	NR_073010.2	n.343+63558A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX53	ENST00000327968.7	c.423T>A	p.Asn141Lys	missense_variant	1/1	6	NM_182699.4	ENSP00000368667.2
ENSG00000289084	ENST00000687119.1	n.83-56332A>T		intron_variant
ENSG00000289084	ENST00000687248.1	n.343+63558A>T		intron_variant

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 23

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

Mar 30, 2024

The c.423T>A (p.N141K) alteration is located in exon 1 (coding exon 1) of the DDX53 gene. This alteration results from a T to A substitution at nucleotide position 423, causing the asparagine (N) at amino acid position 141 to be replaced by a lysine (K). 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	0.094
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.97
DANN	Benign	0.68
DEOGEN2	Benign	0.0034	T
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.068
Sift	Benign	0.41	T
Sift4G	Benign	0.86	T
Polyphen		0.0020	B
Vest4		0.081
MutPred		0.50		Gain of ubiquitination at N141 (P = 0.0051);
MVP		0.068
MPC		0.10
ClinPred		0.055	T
GERP RS		-3.6
Varity_R		0.058
gMVP		0.30

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: chrX-23018597;