Variant 4-168246573-C-T 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.4009G>A(p.Val1337Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000849 in 1,614,064 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000070 ( 1 hom. )

Consequence

DDX60
NM_017631.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.65

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 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=0.06472513).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DDX60	NM_017631.6 linkuse as main transcript	c.4009G>A	p.Val1337Ile	missense_variant	30/38	ENST00000393743.8	NP_060101.3
DDX60	NM_001410861.1 linkuse as main transcript	c.4009G>A	p.Val1337Ile	missense_variant	30/38		NP_001397790.1
DDX60	XM_024454132.2 linkuse as main transcript	c.4009G>A	p.Val1337Ile	missense_variant	31/39		XP_024309900.1
DDX60	XM_024454133.2 linkuse as main transcript	c.4009G>A	p.Val1337Ile	missense_variant	30/38		XP_024309901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
DDX60	ENST00000393743.8 linkuse as main transcript	c.4009G>A	p.Val1337Ile	missense_variant	30/38	1	NM_017631.6	ENSP00000377344	P2
DDX60	ENST00000680771.1 linkuse as main transcript	c.4009G>A	p.Val1337Ile	missense_variant	30/38			ENSP00000505292	A2
DDX60	ENST00000679510.1 linkuse as main transcript	c.4009G>A	p.Val1337Ile	missense_variant, NMD_transcript_variant	30/39			ENSP00000506501

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000821

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000120

AC:

AN:

250838

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

135540

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.000145

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:

0.0000530

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.0000698

AC:

102

AN:

1461792

Hom.:

Cov.:

AF XY:

0.0000688

AC XY:

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.00167

Gnomad4 AMR exome

AF:

0.000134

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:

0.0000189

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.000230

AC:

AN:

152272

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000818

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000814

Hom.:

Bravo

AF:

0.000340

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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 16, 2022

The c.4009G>A (p.V1337I) alteration is located in exon 30 (coding exon 29) of the DDX60 gene. This alteration results from a G to A substitution at nucleotide position 4009, causing the valine (V) at amino acid position 1337 to be replaced by an isoleucine (I). 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

0.12

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.033

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.73

M_CAP

Benign

0.021

MetaRNN

Benign

0.065

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

0.95

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.82

REVEL

Benign

0.11

Sift

Benign

0.047

Sift4G

Benign

0.075

Polyphen

0.98

Vest4

0.30

MVP

0.46

MPC

0.35

ClinPred

0.021

GERP RS

5.8

Varity_R

0.14

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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