X-23001200-G-T

Variant names:

• chrX-23001200-G-T
• rs5925720
• NM_182699.4:c.1143G>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_182699.4(DDX53):​c.1143G>T​(p.Met381Ile) variant causes a missense change. The variant allele was found at a frequency of 0.124 in 1,209,264 control chromosomes in the GnomAD database, including 7,139 homozygotes. There are 52,794 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.099 (527 hom., 3523 hem., cov: 23)
  • Exomes 𝑓: 0.13 (6612 hom. 49271 hem.)
• Consequence: DDX53 NM_182699.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 5.52
• Publications: 11 publications found

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]

PTCHD1-AS (HGNC:37703): (PTCHD1 antisense RNA (head to head))

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001996249).
• BP6: Variant X-23001200-G-T is Benign according to our data. Variant chrX-23001200-G-T is described in ClinVar as Benign. ClinVar VariationId is 3055488.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182699.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX53	NM_182699.4	MANE Select	c.1143G>T	p.Met381Ile	missense	Exon 1 of 1	NP_874358.2	Q86TM3
	PTCHD1-AS	NR_073010.2		n.343+62838C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX53	ENST00000327968.7	TSL:6 MANE Select	c.1143G>T	p.Met381Ile	missense	Exon 1 of 1	ENSP00000368667.2	Q86TM3
	PTCHD1-AS	ENST00000687119.1		n.83-57052C>A		intron	N/A
	PTCHD1-AS	ENST00000687248.2		n.371+62838C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0986 AC: 10992 AN: 111476 Hom.: 528 Cov.: 23

Gnomad AFR AF: 0.0178

Gnomad AMI AF: 0.0486

Gnomad AMR AF: 0.0847

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.103

GnomAD2 exomes AF: 0.146 AC: 26594 AN: 182773 AF XY: 0.162

Gnomad AFR exome AF: 0.0149

Gnomad AMR exome AF: 0.101

Gnomad ASJ exome AF: 0.139

Gnomad EAS exome AF: 0.255

Gnomad FIN exome AF: 0.177

Gnomad NFE exome AF: 0.114

Gnomad OTH exome AF: 0.134

GnomAD4 exome AF: 0.127 AC: 139329 AN: 1097733 Hom.: 6612 Cov.: 32 AF XY: 0.136 AC XY: 49271 AN XY: 363145

African (AFR) AF: 0.0141 AC: 372 AN: 26395

American (AMR) AF: 0.0979 AC: 3444 AN: 35173

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 2727 AN: 19377

East Asian (EAS) AF: 0.239 AC: 7223 AN: 30189

South Asian (SAS) AF: 0.327 AC: 17693 AN: 54050

European-Finnish (FIN) AF: 0.177 AC: 7170 AN: 40506

Middle Eastern (MID) AF: 0.128 AC: 530 AN: 4133

European-Non Finnish (NFE) AF: 0.112 AC: 93956 AN: 841826

Other (OTH) AF: 0.135 AC: 6214 AN: 46084

GnomAD4 genome AF: 0.0985 AC: 10988 AN: 111531 Hom.: 527 Cov.: 23 AF XY: 0.104 AC XY: 3523 AN XY: 33737

African (AFR) AF: 0.0177 AC: 546 AN: 30821

American (AMR) AF: 0.0846 AC: 894 AN: 10562

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 408 AN: 2646

East Asian (EAS) AF: 0.256 AC: 896 AN: 3505

South Asian (SAS) AF: 0.340 AC: 886 AN: 2606

European-Finnish (FIN) AF: 0.184 AC: 1086 AN: 5913

Middle Eastern (MID) AF: 0.110 AC: 24 AN: 219

European-Non Finnish (NFE) AF: 0.114 AC: 6058 AN: 53059

Other (OTH) AF: 0.103 AC: 157 AN: 1521

Alfa AF: 0.113 Hom.: 11018

Bravo AF: 0.0860

TwinsUK AF: 0.104 AC: 387

ALSPAC AF: 0.116 AC: 336

ESP6500AA AF: 0.0175 AC: 67

ESP6500EA AF: 0.117 AC: 789

ExAC AF: 0.149 AC: 18142

EpiCase AF: 0.113

EpiControl AF: 0.116

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	DDX53-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.63
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.94	D
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.5
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.38
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.15
MutPred		0.26		Gain of methylation at K380 (P = 0.0255)
MPC		0.51
ClinPred		0.024	T
GERP RS		4.3
Varity_R		0.98
gMVP		0.67
Mutation Taster		=90/10	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5925720; hg19: chrX-23019317; COSMIC: COSV60068499;