Genetic Variant DDX27:p.Gly175Val (chr20-49225123-G-T) – ACMG Classification: Benign (-12 pts)

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

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]

DDX27 links:

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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
DDX27	NM_017895.8 link	c.524G>T	p.Gly175Val	missense_variant	Exon 6 of 21	ENST00000618172.5	NP_060365.8
DDX27	NM_001348187.2 link	c.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
DDX27	ENST00000618172.5 link	c.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.:

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.:

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.:

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

BayesDel_noAF

Benign

-0.53

CADD

Benign

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

LIST_S2

Uncertain

0.89

D;.;D

MetaRNN

Benign

0.0014

T;T;T

MetaSVM

Benign

-0.70

MutationAssessor

Benign

1.9

L;L;.

PrimateAI

Benign

0.41

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over