Variant 4-168255724-T-G 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.3544A>C(p.Lys1182Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000418 in 1,436,508 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: not found (cov: 32)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

DDX60
NM_017631.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.09

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:

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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=0.19205701).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DDX60	NM_017631.6 linkuse as main transcript	c.3544A>C	p.Lys1182Gln	missense_variant	26/38	ENST00000393743.8	NP_060101.3
DDX60	NM_001410861.1 linkuse as main transcript	c.3544A>C	p.Lys1182Gln	missense_variant	26/38		NP_001397790.1
DDX60	XM_024454132.2 linkuse as main transcript	c.3544A>C	p.Lys1182Gln	missense_variant	27/39		XP_024309900.1
DDX60	XM_024454133.2 linkuse as main transcript	c.3544A>C	p.Lys1182Gln	missense_variant	26/38		XP_024309901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX60	ENST00000393743.8 linkuse as main transcript	c.3544A>C	p.Lys1182Gln	missense_variant	26/38	1	NM_017631.6	ENSP00000377344	P2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000418

AC:

AN:

1436508

Hom.:

Cov.:

AF XY:

0.00000560

AC XY:

AN XY:

714146

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:

0.00

Gnomad4 NFE exome

AF:

0.00000543

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Sep 13, 2023

The c.3544A>C (p.K1182Q) alteration is located in exon 26 (coding exon 25) of the DDX60 gene. This alteration results from a A to C substitution at nucleotide position 3544, causing the lysine (K) at amino acid position 1182 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

0.17

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.024

Eigen

Benign

0.15

Eigen_PC

Benign

0.063

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.75

M_CAP

Benign

0.039

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

1.0

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.18

Sift

Benign

0.030

Sift4G

Uncertain

0.045

Polyphen

0.97

Vest4

0.16

MutPred

0.39

Gain of glycosylation at S1179 (P = 0.003);

MVP

0.35

MPC

0.38

ClinPred

0.94

GERP RS

5.1

Varity_R

0.46

gMVP

0.18

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