Variant chr20-49228778-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017895.8(DDX27):c.770C>T(p.Pro257Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DDX27
NM_017895.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.81

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23409909).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX27	NM_017895.8 link	c.770C>T	p.Pro257Leu	missense_variant	8/21	ENST00000618172.5	NP_060365.8
DDX27	NM_001348187.2 link	c.770C>T	p.Pro257Leu	missense_variant	8/22		NP_001335116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DDX27	ENST00000618172.5 link	c.770C>T	p.Pro257Leu	missense_variant	8/21	1	NM_017895.8	ENSP00000482680.1	B7Z6D5
DDX27	ENST00000484427.5 link	n.872C>T		non_coding_transcript_exon_variant	8/19	1
DDX27	ENST00000493252.2 link	c.293C>T	p.Pro98Leu	missense_variant	4/8	3		ENSP00000483119.1	A0A087X059

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250710

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135542

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461108

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726764

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 10, 2024

The c.863C>T (p.P288L) alteration is located in exon 8 (coding exon 8) of the DDX27 gene. This alteration results from a C to T substitution at nucleotide position 863, causing the proline (P) at amino acid position 288 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.095

T;T;T

Eigen

Benign

-0.053

Eigen_PC

Benign

0.036

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.96

D;.;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

L;L;.

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-3.2

.;D;.

REVEL

Benign

0.14

Sift

Uncertain

0.010

.;D;.

Sift4G

Uncertain

0.024

D;D;D

Polyphen

0.083

B;B;.

Vest4

0.29

MutPred

0.43

Loss of relative solvent accessibility (P = 0.0186);Loss of relative solvent accessibility (P = 0.0186);.;

MVP

0.41

MPC

0.49

ClinPred

0.89

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.14

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over