Variant 17-5450253-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020162.4(DHX33):c.1678A>G(p.Met560Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000524 in 1,614,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00055 ( 0 hom. )

Consequence

DHX33
NM_020162.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.140

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:

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ACMG classification

Classification made for transcript

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=0.06085661).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DHX33	NM_020162.4 linkuse as main transcript	c.1678A>G	p.Met560Val	missense_variant	10/12	ENST00000225296.8	NP_064547.2
DHX33	NM_001199699.2 linkuse as main transcript	c.1159A>G	p.Met387Val	missense_variant	9/11		NP_001186628.1
DHX33	XM_047436418.1 linkuse as main transcript	c.1550A>G	p.His517Arg	missense_variant	9/9		XP_047292374.1
DHX33	XM_017024877.2 linkuse as main transcript	c.394A>G	p.Met132Val	missense_variant	6/8		XP_016880366.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHX33	ENST00000225296.8 linkuse as main transcript	c.1678A>G	p.Met560Val	missense_variant	10/12	1	NM_020162.4	ENSP00000225296	P1	Q9H6R0-1

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000514

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000163

AC:

AN:

251492

Hom.:

AF XY:

0.000162

AC XY:

AN XY:

135922

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:

0.00

Gnomad NFE exome

AF:

0.000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000551

AC:

806

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000525

AC XY:

382

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000687

Gnomad4 OTH exome

AF:

0.000613

GnomAD4 genome

AF:

0.000256

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000514

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000564

Hom.:

Bravo

AF:

0.000257

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000173

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000474

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

Jul 09, 2021

The c.1678A>G (p.M560V) alteration is located in exon 10 (coding exon 10) of the DHX33 gene. This alteration results from a A to G substitution at nucleotide position 1678, causing the methionine (M) at amino acid position 560 to be replaced by a valine (V). 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

0.062

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.60

DANN

Benign

0.62

DEOGEN2

Benign

0.0064

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.0050

MetaRNN

Benign

0.061

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.76

N;.

MutationTaster

Benign

0.98

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

0.74

N;N

REVEL

Benign

0.053

Sift

Benign

0.15

T;T

Sift4G

Benign

0.48

T;T

Polyphen

0.0

B;B

Vest4

0.31

MVP

0.23

MPC

0.24

ClinPred

0.034

GERP RS

-6.5

Varity_R

0.025

gMVP

0.43

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