20-49225123-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017895.8(DDX27):​c.524G>T​(p.Gly175Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,612,734 control chromosomes in the GnomAD database, including 33,994 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.20 ( 2961 hom., cov: 32)
Exomes 𝑓: 0.20 ( 31033 hom. )

Consequence

DDX27
NM_017895.8 missense

Scores

2
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.49
Variant links:
Genes affected
DDX27 (HGNC:15837): (DEAD-box helicase 27) 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 involved in the processing of 5.8S and 28S ribosomal RNAs. More specifically, the encoded protein localizes to the nucleolus, where it interacts with the PeBoW complex to ensure proper 3' end formation of 47S rRNA. [provided by RefSeq, Jan 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0014153719).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DDX27NM_017895.8 linkc.524G>T p.Gly175Val missense_variant Exon 6 of 21 ENST00000618172.5 NP_060365.8
DDX27NM_001348187.2 linkc.524G>T p.Gly175Val missense_variant Exon 6 of 22 NP_001335116.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DDX27ENST00000618172.5 linkc.524G>T p.Gly175Val missense_variant Exon 6 of 21 1 NM_017895.8 ENSP00000482680.1 B7Z6D5

Frequencies

GnomAD3 genomes
AF:
0.195
AC:
29684
AN:
151938
Hom.:
2960
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.200
Gnomad AMI
AF:
0.363
Gnomad AMR
AF:
0.160
Gnomad ASJ
AF:
0.162
Gnomad EAS
AF:
0.0522
Gnomad SAS
AF:
0.0858
Gnomad FIN
AF:
0.215
Gnomad MID
AF:
0.136
Gnomad NFE
AF:
0.217
Gnomad OTH
AF:
0.159
GnomAD3 exomes
AF:
0.174
AC:
43867
AN:
251472
Hom.:
4223
AF XY:
0.171
AC XY:
23258
AN XY:
135910
show subpopulations
Gnomad AFR exome
AF:
0.194
Gnomad AMR exome
AF:
0.167
Gnomad ASJ exome
AF:
0.166
Gnomad EAS exome
AF:
0.0416
Gnomad SAS exome
AF:
0.0835
Gnomad FIN exome
AF:
0.212
Gnomad NFE exome
AF:
0.213
Gnomad OTH exome
AF:
0.180
GnomAD4 exome
AF:
0.201
AC:
293482
AN:
1460678
Hom.:
31033
Cov.:
32
AF XY:
0.197
AC XY:
143085
AN XY:
726658
show subpopulations
Gnomad4 AFR exome
AF:
0.196
Gnomad4 AMR exome
AF:
0.165
Gnomad4 ASJ exome
AF:
0.168
Gnomad4 EAS exome
AF:
0.0664
Gnomad4 SAS exome
AF:
0.0830
Gnomad4 FIN exome
AF:
0.212
Gnomad4 NFE exome
AF:
0.218
Gnomad4 OTH exome
AF:
0.184
GnomAD4 genome
AF:
0.195
AC:
29700
AN:
152056
Hom.:
2961
Cov.:
32
AF XY:
0.190
AC XY:
14150
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.200
Gnomad4 AMR
AF:
0.160
Gnomad4 ASJ
AF:
0.162
Gnomad4 EAS
AF:
0.0521
Gnomad4 SAS
AF:
0.0871
Gnomad4 FIN
AF:
0.215
Gnomad4 NFE
AF:
0.217
Gnomad4 OTH
AF:
0.160
Alfa
AF:
0.204
Hom.:
5950
Bravo
AF:
0.189
TwinsUK
AF:
0.217
AC:
803
ALSPAC
AF:
0.217
AC:
835
ESP6500AA
AF:
0.187
AC:
826
ESP6500EA
AF:
0.223
AC:
1918
ExAC
AF:
0.176
AC:
21375
Asia WGS
AF:
0.0920
AC:
320
AN:
3478
EpiCase
AF:
0.205
EpiControl
AF:
0.200

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.071
BayesDel_addAF
Benign
-0.63
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
22
DANN
Benign
0.97
DEOGEN2
Benign
0.010
T;T;T
Eigen
Benign
-0.096
Eigen_PC
Benign
0.049
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.89
D;.;D
MetaRNN
Benign
0.0014
T;T;T
MetaSVM
Benign
-0.70
T
MutationAssessor
Benign
1.9
L;L;.
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-0.93
.;N;.
REVEL
Benign
0.11
Sift
Benign
0.15
.;T;.
Sift4G
Benign
0.27
T;T;T
Polyphen
0.048
B;B;.
Vest4
0.11
MPC
0.25
ClinPred
0.0081
T
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.2
Varity_R
0.22
gMVP
0.24

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs11553387; hg19: chr20-47841660; COSMIC: COSV65629728; API