Variant 4-168220692-A-C 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_017631.6(DDX60):c.5002T>G(p.Leu1668Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000428 in 1,450,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

DDX60
NM_017631.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.256

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:

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=0.10209331).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX60	NM_017631.6 linkuse as main transcript	c.5002T>G	p.Leu1668Val	missense_variant	37/38	ENST00000393743.8	NP_060101.3	Q8IY21Q9H616A0A3G9HN97Q9NXV7Q6B0F7
DDX60	NM_001410861.1 linkuse as main transcript	c.5002T>G	p.Leu1668Val	missense_variant	37/38		NP_001397790.1
DDX60	XM_024454132.2 linkuse as main transcript	c.5002T>G	p.Leu1668Val	missense_variant	38/39		XP_024309900.1
DDX60	XM_024454133.2 linkuse as main transcript	c.5002T>G	p.Leu1668Val	missense_variant	37/38		XP_024309901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX60	ENST00000393743.8 linkuse as main transcript	c.5002T>G	p.Leu1668Val	missense_variant	37/38	1	NM_017631.6	ENSP00000377344.3		Q8IY21

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000415

AC:

AN:

168478

Hom.:

AF XY:

0.0000638

AC XY:

AN XY:

94092

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:

0.00

Gnomad FIN exome

AF:

0.0000513

Gnomad NFE exome

AF:

0.0000712

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000439

AC:

AN:

1297992

Hom.:

Cov.:

AF XY:

0.0000451

AC XY:

AN XY:

643110

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:

0.00

Gnomad4 FIN exome

AF:

0.0000206

Gnomad4 NFE exome

AF:

0.0000525

Gnomad4 OTH exome

AF:

0.0000378

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000109

Hom.:

Bravo

AF:

0.0000869

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.0000495

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

Aug 12, 2024

The c.5002T>G (p.L1668V) alteration is located in exon 37 (coding exon 36) of the DDX60 gene. This alteration results from a T to G substitution at nucleotide position 5002, causing the leucine (L) at amino acid position 1668 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

0.10

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.44

CADD

Benign

4.0

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.68

M_CAP

Benign

0.020

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.8

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.8

REVEL

Benign

0.075

Sift

Benign

0.18

Sift4G

Benign

0.25

Polyphen

0.88

Vest4

0.23

MVP

0.17

MPC

0.35

ClinPred

0.32

GERP RS

-0.50

Varity_R

0.066

gMVP

0.13

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