X-23000242-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_182699.4(DDX53):c.185T>C(p.Val62Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 1,186,662 control chromosomes in the GnomAD database, including 825 homozygotes. There are 3,507 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.055 (409 hom., 1644 hem., cov: 24)
  • Exomes 𝑓: 0.0065 (416 hom. 1863 hem.)
• Consequence: DDX53 NM_182699.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.862

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0020723045).
• BP6: Variant X-23000242-T-C is Benign according to our data. Variant chrX-23000242-T-C is described in ClinVar as [Benign]. Clinvar id is 3055405.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX53	NM_182699.4	c.185T>C	p.Val62Ala	missense_variant	1/1	ENST00000327968.7
PTCHD1-AS	NR_073010.2	n.343+63796A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX53	ENST00000327968.7	c.185T>C	p.Val62Ala	missense_variant	1/1		NM_182699.4	P1
	ENST00000687248.1	n.343+63796A>G		intron_variant, non_coding_transcript_variant
	ENST00000687119.1	n.83-56094A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0544 AC: 6095 AN: 112006 Hom.: 407 Cov.: 24 AF XY: 0.0477 AC XY: 1634 AN XY: 34228

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0266

Gnomad ASJ AF: 0.00188

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00147

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0335

Gnomad NFE AF: 0.000751

Gnomad OTH AF: 0.0463

GnomAD3 exomes AF: 0.0184 AC: 2993 AN: 162380 Hom.: 223 AF XY: 0.0132 AC XY: 684 AN XY: 51900

Gnomad AFR exome AF: 0.200

Gnomad AMR exome AF: 0.0131

Gnomad ASJ exome AF: 0.00140

Gnomad EAS exome AF: 0.0000772

Gnomad SAS exome AF: 0.000594

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000830

Gnomad OTH exome AF: 0.00899

GnomAD4 exome AF: 0.00646 AC: 6946 AN: 1074602 Hom.: 416 Cov.: 31 AF XY: 0.00538 AC XY: 1863 AN XY: 346128

Gnomad4 AFR exome AF: 0.203

Gnomad4 AMR exome AF: 0.0152

Gnomad4 ASJ exome AF: 0.00105

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000688

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000491

Gnomad4 OTH exome AF: 0.0168

GnomAD4 genome AF: 0.0546 AC: 6115 AN: 112060 Hom.: 409 Cov.: 24 AF XY: 0.0479 AC XY: 1644 AN XY: 34292

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.0266

Gnomad4 ASJ AF: 0.00188

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00147

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000733

Gnomad4 OTH AF: 0.0470

Alfa AF: 0.00707 Hom.: 418

Bravo AF: 0.0642

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000692 AC: 2

ESP6500AA AF: 0.187 AC: 719

ESP6500EA AF: 0.000595 AC: 4

ExAC AF: 0.0180 AC: 2177

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

DDX53-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 25, 2019

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.97	T
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.0070
Dann	Benign	0.53
DEOGEN2	Benign	0.0032	T
FATHMM_MKL	Benign	0.0027	N
LIST_S2	Benign	0.19	T
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.42	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.43	T
PROVEAN	Benign	1.8	N
REVEL	Benign	0.027
Sift	Benign	0.48	T
Sift4G	Benign	0.82	T
Polyphen		0.0010	B
Vest4		0.016
MPC		0.11
ClinPred		0.0055	T
GERP RS		-4.1
Varity_R		0.021
gMVP		0.36

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: rs4412516; hg19: chrX-23018359;