4-168246470-C-T

Variant summary

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

The NM_017631.6(DDX60):​c.4112G>A​(p.Arg1371Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,614,006 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 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

DDX60
NM_017631.6 missense

Scores

5
4
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.63
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]

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=0.18485808).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DDX60NM_017631.6 linkuse as main transcriptc.4112G>A p.Arg1371Gln missense_variant 30/38 ENST00000393743.8 NP_060101.3
DDX60NM_001410861.1 linkuse as main transcriptc.4112G>A p.Arg1371Gln missense_variant 30/38 NP_001397790.1
DDX60XM_024454132.2 linkuse as main transcriptc.4112G>A p.Arg1371Gln missense_variant 31/39 XP_024309900.1
DDX60XM_024454133.2 linkuse as main transcriptc.4112G>A p.Arg1371Gln missense_variant 30/38 XP_024309901.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DDX60ENST00000393743.8 linkuse as main transcriptc.4112G>A p.Arg1371Gln missense_variant 30/381 NM_017631.6 ENSP00000377344 P2
DDX60ENST00000680771.1 linkuse as main transcriptc.4112G>A p.Arg1371Gln missense_variant 30/38 ENSP00000505292 A2
DDX60ENST00000679510.1 linkuse as main transcriptc.4112G>A p.Arg1371Gln missense_variant, NMD_transcript_variant 30/39 ENSP00000506501

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152100
Hom.:
0
Cov.:
32
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:
0.000771
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:
0.0000319
AC:
8
AN:
250928
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135600
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000436
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000958
AC:
14
AN:
1461788
Hom.:
0
Cov.:
31
AF XY:
0.0000110
AC XY:
8
AN XY:
727196
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000202
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152218
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74406
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000773
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189
ExAC
AF:
0.0000412
AC:
5

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 submitterclinical testingAmbry GeneticsFeb 28, 2023The c.4112G>A (p.R1371Q) 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 4112, causing the arginine (R) at amino acid position 1371 to be replaced by a glutamine (Q). 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
0.31
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.12
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.19
T
Eigen
Pathogenic
0.69
Eigen_PC
Uncertain
0.66
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Uncertain
0.94
D
M_CAP
Benign
0.039
D
MetaRNN
Benign
0.18
T
MetaSVM
Benign
-0.81
T
MutationAssessor
Pathogenic
3.3
M
MutationTaster
Benign
0.98
D
PrimateAI
Benign
0.41
T
PROVEAN
Uncertain
-3.9
D
REVEL
Benign
0.25
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.36
MVP
0.44
MPC
0.71
ClinPred
0.97
D
GERP RS
5.8
Varity_R
0.71
gMVP
0.71

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.

Other links and lift over

dbSNP: rs193196668; hg19: chr4-169167621; API