6-30655493-C-T
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_003587.5(DHX16):c.2603G>A(p.Arg868His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,613,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000015 ( 0 hom. )
Consequence
DHX16
NM_003587.5 missense
NM_003587.5 missense
Scores
7
11
Clinical Significance
Conservation
PhyloP100: 2.24
Genes affected
DHX16 (HGNC:2739): (DEAH-box helicase 16) DEAD box proteins, 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 family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which is a functional homolog of fission yeast Prp8 protein involved in cell cycle progression. This gene is mapped to the MHC region on chromosome 6p21.3, a region where many malignant, genetic and autoimmune disease genes are linked. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2018]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DHX16. . Gene score misZ 3.0787 (greater than the threshold 3.09). Trascript score misZ 4.2489 (greater than threshold 3.09). GenCC has associacion of gene with neuromuscular disease and ocular or auditory anomalies with or without seizures.
BP4
Computational evidence support a benign effect (MetaRNN=0.22315195).
BS2
High AC in GnomAdExome4 at 22 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DHX16 | NM_003587.5 | c.2603G>A | p.Arg868His | missense_variant | 17/20 | ENST00000376442.8 | NP_003578.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DHX16 | ENST00000376442.8 | c.2603G>A | p.Arg868His | missense_variant | 17/20 | 1 | NM_003587.5 | ENSP00000365625.3 | ||
DHX16 | ENST00000376437.9 | c.1160G>A | p.Arg387His | missense_variant | 9/12 | 1 | ENSP00000365620.5 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152216Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000202 AC: 5AN: 247072Hom.: 0 AF XY: 0.0000297 AC XY: 4AN XY: 134564
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GnomAD4 exome AF: 0.0000151 AC: 22AN: 1460938Hom.: 0 Cov.: 32 AF XY: 0.0000165 AC XY: 12AN XY: 726778
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152334Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74492
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 09, 2024 | The c.2603G>A (p.R868H) alteration is located in exon 17 (coding exon 17) of the DHX16 gene. This alteration results from a G to A substitution at nucleotide position 2603, causing the arginine (R) at amino acid position 868 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;N
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
P;D
Vest4
MVP
MPC
0.74
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at