X-23000547-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_182699.4(DDX53):c.490G>A(p.Glu164Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,209,165 control chromosomes in the GnomAD database, including 2 homozygotes. There are 478 hemizygotes in GnomAD. 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 Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00081 (0 hom., 27 hem., cov: 23)
  • Exomes 𝑓: 0.0013 (2 hom. 451 hem.)
• Consequence: DDX53 NM_182699.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0540

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 Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0089791715).
• BP6: Variant X-23000547-G-A is Benign according to our data. Variant chrX-23000547-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 717072.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-23000547-G-A is described in Lovd as [Likely_benign].
• BS2: High Hemizygotes in GnomAd at 28 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX53	NM_182699.4	c.490G>A	p.Glu164Lys	missense_variant	1/1	ENST00000327968.7
PTCHD1-AS	NR_073010.2	n.343+63491C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX53	ENST00000327968.7	c.490G>A	p.Glu164Lys	missense_variant	1/1		NM_182699.4	P1
	ENST00000687248.1	n.343+63491C>T		intron_variant, non_coding_transcript_variant
	ENST00000687119.1	n.83-56399C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.000817 AC: 91 AN: 111410 Hom.: 0 Cov.: 23 AF XY: 0.000831 AC XY: 28 AN XY: 33692

Gnomad AFR AF: 0.000196

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000190

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00116

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00143

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000642 AC: 117 AN: 182349 Hom.: 0 AF XY: 0.000583 AC XY: 39 AN XY: 66867

Gnomad AFR exome AF: 0.000152

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000537

Gnomad FIN exome AF: 0.00156

Gnomad NFE exome AF: 0.00105

Gnomad OTH exome AF: 0.000666

GnomAD4 exome AF: 0.00128 AC: 1403 AN: 1097700 Hom.: 2 Cov.: 32 AF XY: 0.00124 AC XY: 451 AN XY: 363070

Gnomad4 AFR exome AF: 0.000189

Gnomad4 AMR exome AF: 0.000114

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000185

Gnomad4 FIN exome AF: 0.000987

Gnomad4 NFE exome AF: 0.00153

Gnomad4 OTH exome AF: 0.00132

GnomAD4 genome AF: 0.000807 AC: 90 AN: 111465 Hom.: 0 Cov.: 23 AF XY: 0.000800 AC XY: 27 AN XY: 33757

Gnomad4 AFR AF: 0.000196

Gnomad4 AMR AF: 0.000190

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00116

Gnomad4 NFE AF: 0.00141

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00120 Hom.: 60

Bravo AF: 0.000718

TwinsUK AF: 0.00162 AC: 6

ALSPAC AF: 0.00173 AC: 5

ESP6500AA AF: 0.000261 AC: 1

ESP6500EA AF: 0.00193 AC: 13

ExAC AF: 0.000560 AC: 68

EpiCase AF: 0.000927

EpiControl AF: 0.000830

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

DDX53-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 30, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.85
Cadd	Benign	7.7
Dann	Benign	0.84
DEOGEN2	Benign	0.014	T
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.0090	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.2	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.024
Sift	Benign	0.30	T
Sift4G	Benign	0.57	T
Polyphen		0.089	B
Vest4		0.043
MVP		0.068
MPC		0.10
ClinPred		0.010	T
GERP RS		2.0
Varity_R		0.076
gMVP		0.49

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: rs143131443; hg19: chrX-23018664;