rs539104890

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021931.4(DHX35):​c.649C>G​(p.Arg217Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,451,170 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R217W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

DHX35
NM_021931.4 missense

Scores

5
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.10
Variant links:
Genes affected
DHX35 (HGNC:15861): (DEAH-box helicase 35) 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 the DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. The function of this gene product which is a member of this family, has not been determined. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2010]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DHX35NM_021931.4 linkc.649C>G p.Arg217Gly missense_variant Exon 9 of 22 ENST00000252011.8 NP_068750.2 Q9H5Z1-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DHX35ENST00000252011.8 linkc.649C>G p.Arg217Gly missense_variant Exon 9 of 22 1 NM_021931.4 ENSP00000252011.3 Q9H5Z1-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000138
AC:
2
AN:
1451170
Hom.:
0
Cov.:
30
AF XY:
0.00000277
AC XY:
2
AN XY:
720990
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000181
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.33
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Benign
0.15
.;T;.
Eigen
Benign
-0.039
Eigen_PC
Benign
0.092
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.96
D;D;D
M_CAP
Benign
0.015
T
MetaRNN
Uncertain
0.55
D;D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
.;L;.
PrimateAI
Benign
0.27
T
PROVEAN
Uncertain
-4.0
D;D;D
REVEL
Benign
0.11
Sift
Benign
0.33
T;T;T
Sift4G
Benign
0.33
T;T;T
Polyphen
0.17
.;B;.
Vest4
0.60
MutPred
0.44
Loss of ubiquitination at K215 (P = 0.1154);Loss of ubiquitination at K215 (P = 0.1154);.;
MVP
0.43
MPC
0.28
ClinPred
0.94
D
GERP RS
3.6
Varity_R
0.24
gMVP
0.49

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.20
Details are displayed if max score is > 0.2
DS_AL_spliceai
0.20
Position offset: -6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-37630379; API