chr3-154276196-C-T

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

1
1
17

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]

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
DHX36NM_020865.3 linkc.3002G>A p.Arg1001Gln missense_variant Exon 25 of 25 ENST00000496811.6 NP_065916.2 Q9H2U1-1
DHX36NM_001114397.2 linkc.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 Appris UniProt
DHX36ENST00000496811.6 linkc.3002G>A p.Arg1001Gln missense_variant Exon 25 of 25 1 NM_020865.3 ENSP00000417078.1 Q9H2U1-1
DHX36ENST00000329463.9 linkc.2960G>A p.Arg987Gln missense_variant Exon 25 of 25 1 ENSP00000330113.5 Q9H2U1-2
DHX36ENST00000308361.10 linkc.2915G>A p.Arg972Gln missense_variant Exon 24 of 24 1 ENSP00000309296.6 Q9H2U1-3
DHX36ENST00000495598.1 linkn.552G>A non_coding_transcript_exon_variant Exon 3 of 3 2

Frequencies

GnomAD3 genomes
AF:
0.000329
AC:
50
AN:
151994
Hom.:
0
Cov.:
31
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:
21
AN:
249342
Hom.:
0
AF XY:
0.0000668
AC XY:
9
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:
59
AN:
1460430
Hom.:
0
Cov.:
31
AF XY:
0.0000358
AC XY:
26
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:
50
AN:
152112
Hom.:
0
Cov.:
31
AF XY:
0.000377
AC XY:
28
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.:
0
Bravo
AF:
0.000397
ESP6500AA
AF:
0.00113
AC:
5
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000906
AC:
11

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
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
22
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.018
T;.;.
Eigen
Benign
-0.044
Eigen_PC
Benign
-0.013
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Benign
0.81
T;T;T
M_CAP
Benign
0.0074
T
MetaRNN
Benign
0.014
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L;.;.
PrimateAI
Benign
0.30
T
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
T
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.

Other links and lift over

dbSNP: rs140010768; hg19: chr3-153993985; API