rs201981758

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001012967.3(DDX60L):c.5116G>A(p.Glu1706Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000127 in 1,608,244 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

DDX60L
NM_001012967.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.99

Publications

2 publications found

Variant links:

Genes affected

DDX60L (HGNC:26429): (DExD/H-box 60 like) This gene encodes a member of the DExD/H-box helicase family of proteins, a subset of the super family 2 helicases. Members of the DExD/H-box helicase family share a conserved functional core comprised of two RecA-like globular domains. These domains contain conserved motifs that mediate ATP binding, ATP hydrolysis, nucleic acid binding, and RNA unwinding. In addition to functions in RNA metabolism, members of this family are involved in anti-viral immunity and act as cytosolic sensors of viral nucleic acids. The protein encoded by this gene has been shown to inhibit hepatitis C virus replication in response to interferon stimulation in cell culture. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

DDX60L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0049724877).

BP6

Variant 4-168358152-C-T is Benign according to our data. Variant chr4-168358152-C-T is described in CliVar as Likely_benign. Clinvar id is 3081228.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-168358152-C-T is described in CliVar as Likely_benign. Clinvar id is 3081228.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-168358152-C-T is described in CliVar as Likely_benign. Clinvar id is 3081228.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-168358152-C-T is described in CliVar as Likely_benign. Clinvar id is 3081228.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-168358152-C-T is described in CliVar as Likely_benign. Clinvar id is 3081228.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-168358152-C-T is described in CliVar as Likely_benign. Clinvar id is 3081228.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-168358152-C-T is described in CliVar as Likely_benign. Clinvar id is 3081228.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-168358152-C-T is described in CliVar as Likely_benign. Clinvar id is 3081228.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-168358152-C-T is described in CliVar as Likely_benign. Clinvar id is 3081228.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-168358152-C-T is described in CliVar as Likely_benign. Clinvar id is 3081228.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-168358152-C-T is described in CliVar as Likely_benign. Clinvar id is 3081228.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX60L	NM_001012967.3 link	c.5116G>A	p.Glu1706Lys	missense_variant	Exon 38 of 38	ENST00000682922.1	NP_001012985.2	Q5H9U9A0A804HKC9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DDX60L	ENST00000682922.1 link	c.5116G>A	p.Glu1706Lys	missense_variant	Exon 38 of 38		NM_001012967.3	ENSP00000507872.1	A0A804HKC9
DDX60L	ENST00000511577.5 link	c.5116G>A	p.Glu1706Lys	missense_variant	Exon 38 of 38	5		ENSP00000422423.1	Q5H9U9
DDX60L	ENST00000510590.1 link	n.2092G>A		non_coding_transcript_exon_variant	Exon 9 of 9	2
DDX60L	ENST00000513103.1 link	n.416G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000277

AC:

AN:

245606

AF XY:

0.000248

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00460

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000983

Gnomad OTH exome

AF:

0.00117

GnomAD4 exome

AF:

0.000126

AC:

184

AN:

1456128

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

724456

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33290

American (AMR)

AF:

0.0000228

AC:

AN:

43828

Ashkenazi Jewish (ASJ)

AF:

0.00391

AC:

102

AN:

26054

East Asian (EAS)

AF:

0.00

AC:

AN:

39450

South Asian (SAS)

AF:

0.0000703

AC:

AN:

85346

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53104

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.0000478

AC:

AN:

1109160

Other (OTH)

AF:

0.000349

AC:

AN:

60146

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000138

AC:

AN:

152116

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41428

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00374

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000345

Hom.:

Bravo

AF:

0.000136

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000491

AC:

ExAC

AF:

0.000306

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Feb 06, 2023

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.028

(source)

DANN

Benign

0.19

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.00045

M_CAP

Benign

0.0018

MetaRNN

Benign

0.0050

T;T

MetaSVM

Benign

-0.96

PhyloP100

-3.0

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.21

N;N

REVEL

Benign

0.0010

Sift

Benign

0.70

T;T

Sift4G

Pathogenic

0.0

D;D

Vest4

0.059

MVP

0.014

MPC

0.024

ClinPred

0.0032

GERP RS

-2.7

gMVP

0.21

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over