Variant 12-132139730-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_175066.4(DDX51):c.1879C>T(p.Pro627Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000868 in 1,612,988 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: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

DDX51
NM_175066.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.64

Variant links:

Genes affected

DDX51 (HGNC:20082): (DEAD-box helicase 51) Enables RNA binding activity. Predicted to be involved in rRNA processing. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

DDX51 links:

Genome browser will be placed here

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/exons	MANE	UniProt
DDX51	NM_175066.4 linkuse as main transcript	c.1879C>T	p.Pro627Ser	missense_variant	14/15	ENST00000397333.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
DDX51	ENST00000397333.4 linkuse as main transcript	c.1879C>T	p.Pro627Ser	missense_variant	14/15	1	NM_175066.4	P1
DDX51	ENST00000541489.5 linkuse as main transcript	n.525C>T		non_coding_transcript_exon_variant	5/6	1
DDX51	ENST00000462829.2 linkuse as main transcript	n.244C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000241

AC:

AN:

248510

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135234

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.0000869

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:

0.00000890

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1460802

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726700

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.0000671

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.00000827

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

Jan 03, 2024

The c.1879C>T (p.P627S) alteration is located in exon 14 (coding exon 14) of the DDX51 gene. This alteration results from a C to T substitution at nucleotide position 1879, causing the proline (P) at amino acid position 627 to be replaced by a serine (S). 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

0.090

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.023

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.36

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.59

M_CAP

Benign

0.045

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.76

MutationAssessor

Benign

0.26

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.15

Sift

Benign

0.069

Sift4G

Benign

0.36

Polyphen

0.027

Vest4

0.48

MutPred

0.26

Gain of MoRF binding (P = 0.054);

MVP

0.23

MPC

0.042

ClinPred

0.069

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.087

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.37

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.37

Position offset: -12

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