12-113159023-G-A

Position:

chr12-113159023-G-A

Variant summary

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

The NM_024072.4(DDX54):c.2500C>T(p.Arg834Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000453 in 1,611,494 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 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

DDX54
NM_024072.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.90

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 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=0.24660146).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX54	NM_024072.4 linkuse as main transcript	c.2500C>T	p.Arg834Cys	missense_variant	20/20	ENST00000306014.10	NP_076977.3	Q8TDD1-1
CFAP73	NM_001144872.3 linkuse as main transcript	c.*334G>A		3_prime_UTR_variant	8/8	ENST00000335621.11	NP_001138344.1	A6NFT4
DDX54	NM_001111322.2 linkuse as main transcript	c.2503C>T	p.Arg835Cys	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.2500C>T	p.Arg834Cys	missense_variant	20/20	1	NM_024072.4	ENSP00000304072.5		Q8TDD1-1
CFAP73	ENST00000335621.11 linkuse as main transcript	c.*334G>A		3_prime_UTR_variant	8/8	5	NM_001144872.3	ENSP00000333915.6		A6NFT4

Frequencies

GnomAD3 genomes

AF:

0.0000525

AC:

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000964

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000290

AC:

AN:

241662

Hom.:

AF XY:

0.0000380

AC XY:

AN XY:

131594

show subpopulations

Gnomad AFR exome

AF:

0.0000653

Gnomad AMR exome

AF:

0.00

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:

0.0000464

Gnomad OTH exome

AF:

0.000168

GnomAD4 exome

AF:

0.0000445

AC:

AN:

1459230

Hom.:

Cov.:

AF XY:

0.0000441

AC XY:

AN XY:

725806

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.0000224

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:

0.0000486

Gnomad4 OTH exome

AF:

0.0000830

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0000964

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000453

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

See cases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

New York Genome Center

May 05, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.49

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

.;T

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.25

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

.;M

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-3.8

D;D

REVEL

Benign

0.097

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.0070

D;D

Polyphen

0.99

D;D

Vest4

0.14

MVP

0.42

MPC

0.44

ClinPred

0.79

GERP RS

3.1

Varity_R

0.16

gMVP

0.16

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