chr12-113159061-G-A

Position:

chr12-113159061-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_024072.4(DDX54):c.2462C>T(p.Pro821Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0604 in 1,608,710 control chromosomes in the GnomAD database, including 3,469 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.050 ( 267 hom., cov: 32)

Exomes 𝑓: 0.062 ( 3202 hom. )

Consequence

DDX54
NM_024072.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 8.80

Variant links:

Genes affected

DDX54 (HGNC:20084): (DEAD-box helicase 54) This gene encodes a member of the DEAD box protein family. 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. The nucleolar protein encoded by this gene interacts in a hormone-dependent manner with nuclear receptors, and represses their transcriptional activity. Alternative splice variants that encode different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

DDX54 links:

CFAP73 (HGNC:37100): (cilia and flagella associated protein 73) Predicted to enable dynein complex binding activity. Predicted to be involved in cilium movement and inner dynein arm assembly. Predicted to be located in axonemal outer doublet and motile cilium. [provided by Alliance of Genome Resources, Apr 2022]

CFAP73 links:

DDX54 (HGNC:):

DDX54 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018016398).

BP6

Variant 12-113159061-G-A is Benign according to our data. Variant chr12-113159061-G-A is described in ClinVar as [Benign]. Clinvar id is 3056831.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX54	NM_024072.4 linkuse as main transcript	c.2462C>T	p.Pro821Leu	missense_variant	20/20	ENST00000306014.10	NP_076977.3	Q8TDD1-1
CFAP73	NM_001144872.3 linkuse as main transcript	c.*372G>A		3_prime_UTR_variant	8/8	ENST00000335621.11	NP_001138344.1	A6NFT4
DDX54	NM_001111322.2 linkuse as main transcript	c.2465C>T	p.Pro822Leu	missense_variant	20/20		NP_001104792.1	Q8TDD1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX54	ENST00000306014.10 linkuse as main transcript	c.2462C>T	p.Pro821Leu	missense_variant	20/20	1	NM_024072.4	ENSP00000304072.5		Q8TDD1-1
CFAP73	ENST00000335621.11 linkuse as main transcript	c.*372G>A		3_prime_UTR_variant	8/8	5	NM_001144872.3	ENSP00000333915.6		A6NFT4

Frequencies

GnomAD3 genomes

AF:

0.0496

AC:

7548

AN:

152222

Hom.:

267

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0119

Gnomad AMI

AF:

0.0702

Gnomad AMR

AF:

0.0591

Gnomad ASJ

AF:

0.0556

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0122

Gnomad FIN

AF:

0.131

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0631

Gnomad OTH

AF:

0.0574

GnomAD3 exomes

AF:

0.0523

AC:

12400

AN:

237312

Hom.:

438

AF XY:

0.0527

AC XY:

6812

AN XY:

129330

show subpopulations

Gnomad AFR exome

AF:

0.0118

Gnomad AMR exome

AF:

0.0440

Gnomad ASJ exome

AF:

0.0621

Gnomad EAS exome

AF:

0.000608

Gnomad SAS exome

AF:

0.0136

Gnomad FIN exome

AF:

0.127

Gnomad NFE exome

AF:

0.0654

Gnomad OTH exome

AF:

0.0566

GnomAD4 exome

AF:

0.0616

AC:

89696

AN:

1456370

Hom.:

3202

Cov.:

AF XY:

0.0607

AC XY:

43960

AN XY:

724144

show subpopulations

Gnomad4 AFR exome

AF:

0.0109

Gnomad4 AMR exome

AF:

0.0448

Gnomad4 ASJ exome

AF:

0.0601

Gnomad4 EAS exome

AF:

0.000656

Gnomad4 SAS exome

AF:

0.0154

Gnomad4 FIN exome

AF:

0.121

Gnomad4 NFE exome

AF:

0.0669

Gnomad4 OTH exome

AF:

0.0594

GnomAD4 genome

AF:

0.0495

AC:

7543

AN:

152340

Hom.:

267

Cov.:

AF XY:

0.0519

AC XY:

3867

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0119

Gnomad4 AMR

AF:

0.0589

Gnomad4 ASJ

AF:

0.0556

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0120

Gnomad4 FIN

AF:

0.131

Gnomad4 NFE

AF:

0.0631

Gnomad4 OTH

AF:

0.0568

Alfa

AF:

0.0587

Hom.:

544

Bravo

AF:

0.0438

TwinsUK

AF:

0.0750

AC:

278

ALSPAC

AF:

0.0656

AC:

253

ESP6500AA

AF:

0.0127

AC:

ESP6500EA

AF:

0.0579

AC:

498

ExAC

AF:

0.0475

AC:

5750

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DDX54-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 11, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0092

.;T

Eigen

Benign

-0.034

Eigen_PC

Benign

0.13

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

D;D

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

.;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.79

N;N

REVEL

Benign

0.10

Sift

Uncertain

0.028

D;D

Sift4G

Benign

0.20

T;T

Polyphen

0.0090

B;B

Vest4

0.047

MPC

0.32

ClinPred

0.018

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.069

gMVP

0.23

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