Variant 4-168262089-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017631.6(DDX60):c.3184T>G(p.Leu1062Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000312 in 1,443,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

DDX60
NM_017631.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.507

Variant links:

Genes affected

DDX60 (HGNC:25942): (DExD/H-box helicase 60) DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases which are implicated in a number of cellular procsses involving RNA binding and alteration of RNA secondary structure. This gene encodes a DEXD/H box RNA helicase that functions as an antiviral factor and promotes RIG-I-like receptor-mediated signaling. [provided by RefSeq, Apr 2017]

DDX60 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.017175198).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX60	NM_017631.6 linkuse as main transcript	c.3184T>G	p.Leu1062Val	missense_variant	24/38	ENST00000393743.8	NP_060101.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX60	ENST00000393743.8 linkuse as main transcript	c.3184T>G	p.Leu1062Val	missense_variant	24/38	1	NM_017631.6	ENSP00000377344	P2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000604

AC:

AN:

231634

Hom.:

AF XY:

0.0000638

AC XY:

AN XY:

125350

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00104

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000370

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000312

AC:

AN:

1443298

Hom.:

Cov.:

AF XY:

0.0000237

AC XY:

AN XY:

717462

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00128

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000542

Gnomad4 OTH exome

AF:

0.000100

GnomAD4 genome

Cov.:

Alfa

AF:

0.000225

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000412

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

Nov 21, 2022

The c.3184T>G (p.L1062V) alteration is located in exon 24 (coding exon 23) of the DDX60 gene. This alteration results from a T to G substitution at nucleotide position 3184, causing the leucine (L) at amino acid position 1062 to be replaced by a valine (V). 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

0.077

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.76

CADD

Benign

6.7

DANN

Benign

0.39

DEOGEN2

Benign

0.0034

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.50

M_CAP

Benign

0.0046

MetaRNN

Benign

0.017

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.60

MutationTaster

Benign

0.99

PrimateAI

Benign

0.36

PROVEAN

Benign

1.2

REVEL

Benign

0.038

Sift

Benign

0.79

Sift4G

Benign

0.75

Polyphen

0.0010

Vest4

0.12

MutPred

0.33

Gain of methylation at K1065 (P = 0.0764);

MVP

0.030

MPC

0.15

ClinPred

0.010

GERP RS

-4.3

Varity_R

0.034

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