17-5450213-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020162.4(DHX33):c.1718G>A(p.Gly573Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 1,614,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

DHX33
NM_020162.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.94

Variant links:

Genes affected

DHX33 (HGNC:16718): (DEAH-box helicase 33) This gene encodes a member of the DEAD box protein family. The DEAD box proteins are characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2010]

DHX33 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21673721).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DHX33	NM_020162.4 linkuse as main transcript	c.1718G>A	p.Gly573Asp	missense_variant	10/12	ENST00000225296.8
DHX33	NM_001199699.2 linkuse as main transcript	c.1199G>A	p.Gly400Asp	missense_variant	9/11
DHX33	XM_017024877.2 linkuse as main transcript	c.434G>A	p.Gly145Asp	missense_variant	6/8
DHX33	XM_047436418.1 linkuse as main transcript	c.1590G>A	p.Arg530=	synonymous_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DHX33	ENST00000225296.8 linkuse as main transcript	c.1718G>A	p.Gly573Asp	missense_variant	10/12	1	NM_020162.4	P1	Q9H6R0-1

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000835

AC:

AN:

251478

Hom.:

AF XY:

0.0000736

AC XY:

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000149

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000158

AC:

231

AN:

1461856

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

117

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000198

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000118

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000194

Hom.:

Bravo

AF:

0.000147

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 20, 2023

The c.1718G>A (p.G573D) alteration is located in exon 10 (coding exon 10) of the DHX33 gene. This alteration results from a G to A substitution at nucleotide position 1718, causing the glycine (G) at amino acid position 573 to be replaced by an aspartic acid (D). 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

0.13

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.45

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.0078

T;T

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.8

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.95

N;N

REVEL

Benign

0.14

Sift

Benign

0.30

T;T

Sift4G

Benign

0.46

T;T

Polyphen

0.010

B;P

Vest4

0.51

MVP

0.59

MPC

0.31

ClinPred

0.24

GERP RS

5.8

Varity_R

0.12

gMVP

0.46

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over