chr3-154276196-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_020865.3(DHX36):c.3002G>A(p.Arg1001Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000676 in 1,612,542 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 0.00033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

DHX36
NM_020865.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.66

Variant links:

Genes affected

DHX36 (HGNC:14410): (DEAH-box helicase 36) This gene is a member of the DEAH-box family of RNA-dependent NTPases which are named after the conserved amino acid sequence Asp-Glu-Ala-His in motif II. The protein encoded by this gene has been shown to enhance the deadenylation and decay of mRNAs with 3'-UTR AU-rich elements (ARE-mRNA). The protein has also been shown to resolve into single strands the highly stable tetramolecular DNA configuration (G4) that can form spontaneously in guanine-rich regions of DNA. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

DHX36 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0143662095).

BS2

High AC in GnomAd4 at 50 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHX36	NM_020865.3 link	c.3002G>A	p.Arg1001Gln	missense_variant	Exon 25 of 25	ENST00000496811.6	NP_065916.2	Q9H2U1-1
DHX36	NM_001114397.2 link	c.2960G>A	p.Arg987Gln	missense_variant	Exon 25 of 25		NP_001107869.1	Q9H2U1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DHX36	ENST00000496811.6 link	c.3002G>A	p.Arg1001Gln	missense_variant	Exon 25 of 25	1	NM_020865.3	ENSP00000417078.1	Q9H2U1-1
DHX36	ENST00000329463.9 link	c.2960G>A	p.Arg987Gln	missense_variant	Exon 25 of 25	1		ENSP00000330113.5	Q9H2U1-2
DHX36	ENST00000308361.10 link	c.2915G>A	p.Arg972Gln	missense_variant	Exon 24 of 24	1		ENSP00000309296.6	Q9H2U1-3
DHX36	ENST00000495598.1 link	n.552G>A		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.000329

AC:

AN:

151994

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00114

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000842

AC:

AN:

249342

Hom.:

AF XY:

0.0000668

AC XY:

AN XY:

134782

show subpopulations

Gnomad AFR exome

AF:

0.00130

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000404

AC:

AN:

1460430

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

726448

show subpopulations

Gnomad4 AFR exome

AF:

0.00162

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000329

AC:

AN:

152112

Hom.:

Cov.:

AF XY:

0.000377

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00113

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.0000703

Hom.:

Bravo

AF:

0.000397

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000906

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3002G>A (p.R1001Q) alteration is located in exon 25 (coding exon 25) of the DHX36 gene. This alteration results from a G to A substitution at nucleotide position 3002, causing the arginine (R) at amino acid position 1001 to be replaced by a glutamine (Q). 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

0.10

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.018

T;.;.

Eigen

Benign

-0.044

Eigen_PC

Benign

-0.013

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.81

T;T;T

M_CAP

Benign

0.0074

MetaRNN

Benign

0.014

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;.;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.14

N;N;N

REVEL

Benign

0.068

Sift

Benign

0.066

T;T;T

Sift4G

Benign

0.51

T;T;T

Polyphen

0.97

D;B;D

Vest4

0.17

MVP

0.39

MPC

0.37

ClinPred

0.059

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.037

gMVP

0.40

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