4-168252625-C-T

Position:

chr4-168252625-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_017631.6(DDX60):c.3589G>A(p.Val1197Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000683 in 1,611,134 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000069 ( 1 hom. )

Consequence

DDX60
NM_017631.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0890

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.025204778).

BP6

Variant 4-168252625-C-T is Benign according to our data. Variant chr4-168252625-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2271540.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DDX60	NM_017631.6 linkuse as main transcript	c.3589G>A	p.Val1197Met	missense_variant	27/38	ENST00000393743.8	NP_060101.3
DDX60	NM_001410861.1 linkuse as main transcript	c.3589G>A	p.Val1197Met	missense_variant	27/38		NP_001397790.1
DDX60	XM_024454132.2 linkuse as main transcript	c.3589G>A	p.Val1197Met	missense_variant	28/39		XP_024309900.1
DDX60	XM_024454133.2 linkuse as main transcript	c.3589G>A	p.Val1197Met	missense_variant	27/38		XP_024309901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
DDX60	ENST00000393743.8 linkuse as main transcript	c.3589G>A	p.Val1197Met	missense_variant	27/38	1	NM_017631.6	ENSP00000377344	P2
DDX60	ENST00000680771.1 linkuse as main transcript	c.3589G>A	p.Val1197Met	missense_variant	27/38			ENSP00000505292	A2
DDX60	ENST00000505393.1 linkuse as main transcript	n.694G>A		non_coding_transcript_exon_variant	6/6	5
DDX60	ENST00000679510.1 linkuse as main transcript	c.3589G>A	p.Val1197Met	missense_variant, NMD_transcript_variant	27/39			ENSP00000506501

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151998

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:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000201

AC:

AN:

249314

Hom.:

AF XY:

0.0000223

AC XY:

AN XY:

134654

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000585

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000100

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000685

AC:

AN:

1459136

Hom.:

Cov.:

AF XY:

0.00000827

AC XY:

AN XY:

725726

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000449

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000937

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151998

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74268

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:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 10, 2022

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

0.082

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.32

DANN

Benign

0.73

DEOGEN2

Benign

0.0011

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0012

LIST_S2

Benign

0.53

M_CAP

Benign

0.011

MetaRNN

Benign

0.025

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

0.99

REVEL

Benign

0.022

Sift

Benign

0.51

Sift4G

Benign

0.39

Polyphen

0.012

Vest4

0.096

MutPred

0.30

Gain of glycosylation at T1194 (P = 0.0197);

MVP

0.12

MPC

0.15

ClinPred

0.017

GERP RS

2.7

Varity_R

0.027

gMVP

0.088

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