16-72096241-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_ModerateBP6_Very_Strong

The ENST00000268482.8(DHX38):​c.84G>A​(p.Lys28=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000275 in 1,614,174 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00089 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00021 ( 1 hom. )

Consequence

DHX38
ENST00000268482.8 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 5.83
Variant links:
Genes affected
DHX38 (HGNC:17211): (DEAH-box helicase 38) 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. The protein encoded by this gene is a member of the DEAD/H box family of splicing factors. This protein resembles yeast Prp16 more closely than other DEAD/H family members. It is an ATPase and essential for the catalytic step II in pre-mRNA splicing process. [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.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.3).
BP6
Variant 16-72096241-G-A is Benign according to our data. Variant chr16-72096241-G-A is described in ClinVar as [Benign]. Clinvar id is 1169701.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-72096241-G-A is described in Lovd as [Benign]. Variant chr16-72096241-G-A is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DHX38NM_014003.4 linkuse as main transcriptc.84G>A p.Lys28= synonymous_variant 2/27 ENST00000268482.8 NP_054722.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DHX38ENST00000268482.8 linkuse as main transcriptc.84G>A p.Lys28= synonymous_variant 2/271 NM_014003.4 ENSP00000268482 P1Q92620-1
DHX38ENST00000566794.5 linkuse as main transcriptc.84G>A p.Lys28= synonymous_variant 2/34 ENSP00000455939
DHX38ENST00000566489.1 linkuse as main transcriptc.84G>A p.Lys28= synonymous_variant 3/44 ENSP00000457887
DHX38ENST00000579387.5 linkuse as main transcriptc.84G>A p.Lys28= synonymous_variant, NMD_transcript_variant 2/125 ENSP00000462149

Frequencies

GnomAD3 genomes
AF:
0.000894
AC:
136
AN:
152198
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00246
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00157
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.000358
AC:
90
AN:
251364
Hom.:
1
AF XY:
0.000324
AC XY:
44
AN XY:
135880
show subpopulations
Gnomad AFR exome
AF:
0.00308
Gnomad AMR exome
AF:
0.000723
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:
0.0000968
Gnomad OTH exome
AF:
0.000652
GnomAD4 exome
AF:
0.000211
AC:
308
AN:
1461858
Hom.:
1
Cov.:
30
AF XY:
0.000213
AC XY:
155
AN XY:
727220
show subpopulations
Gnomad4 AFR exome
AF:
0.00376
Gnomad4 AMR exome
AF:
0.000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000863
Gnomad4 OTH exome
AF:
0.000811
GnomAD4 genome
AF:
0.000893
AC:
136
AN:
152316
Hom.:
0
Cov.:
32
AF XY:
0.00102
AC XY:
76
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.00245
Gnomad4 AMR
AF:
0.00157
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000425
Hom.:
0
Bravo
AF:
0.00109
EpiCase
AF:
0.000109
EpiControl
AF:
0.000178

ClinVar

Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 19, 2024- -
Likely benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
not specified Benign:1
Benign, no assertion criteria providedclinical testingClinical Genetics, Academic Medical Center-- -
DHX38-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesMay 22, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.30
CADD
Benign
9.5
DANN
Benign
0.86
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs34425506; hg19: chr16-72130140; COSMIC: COSV51699079; COSMIC: COSV51699079; API