chr6-30657053-T-C
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The NM_003587.5(DHX16):āc.2047A>Gā(p.Ile683Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000682 in 1,612,914 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 31)
Exomes š: 0.0000068 ( 0 hom. )
Consequence
DHX16
NM_003587.5 missense
NM_003587.5 missense
Scores
2
9
5
Clinical Significance
Conservation
PhyloP100: 4.27
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 -3 ACMG points.
PP2
Missense variant where missense usually causes diseases, DHX16
BS2
High AC in GnomAdExome4 at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DHX16 | NM_003587.5 | c.2047A>G | p.Ile683Val | missense_variant | 13/20 | ENST00000376442.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DHX16 | ENST00000376442.8 | c.2047A>G | p.Ile683Val | missense_variant | 13/20 | 1 | NM_003587.5 | P1 | |
DHX16 | ENST00000376437.9 | c.604A>G | p.Ile202Val | missense_variant | 5/12 | 1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152156Hom.: 0 Cov.: 31
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GnomAD4 exome AF: 0.00000685 AC: 10AN: 1460758Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5AN XY: 726702
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152156Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74326
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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 | Mar 01, 2023 | The c.2047A>G (p.I683V) alteration is located in exon 13 (coding exon 13) of the DHX16 gene. This alteration results from a A to G substitution at nucleotide position 2047, causing the isoleucine (I) at amino acid position 683 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Benign
T;D
Polyphen
D;D
Vest4
MutPred
0.69
.;Loss of helix (P = 0.1706);
MVP
MPC
0.50
ClinPred
D
GERP RS
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