Variant 4-168221770-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017631.6(DDX60):c.4936T>C(p.Tyr1646His) variant causes a missense change. The variant allele was found at a frequency of 0.000044 in 1,613,048 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

DDX60
NM_017631.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.86

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DDX60	NM_017631.6 linkuse as main transcript	c.4936T>C	p.Tyr1646His	missense_variant	36/38	ENST00000393743.8	NP_060101.3
DDX60	NM_001410861.1 linkuse as main transcript	c.4936T>C	p.Tyr1646His	missense_variant	36/38		NP_001397790.1
DDX60	XM_024454132.2 linkuse as main transcript	c.4936T>C	p.Tyr1646His	missense_variant	37/39		XP_024309900.1
DDX60	XM_024454133.2 linkuse as main transcript	c.4936T>C	p.Tyr1646His	missense_variant	36/38		XP_024309901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
DDX60	ENST00000393743.8 linkuse as main transcript	c.4936T>C	p.Tyr1646His	missense_variant	36/38	1	NM_017631.6	ENSP00000377344	P2
DDX60	ENST00000680771.1 linkuse as main transcript	c.4936T>C	p.Tyr1646His	missense_variant	36/38			ENSP00000505292	A2
DDX60	ENST00000511317.2 linkuse as main transcript	c.415T>C	p.Tyr139His	missense_variant	4/5	3		ENSP00000422669
DDX60	ENST00000679510.1 linkuse as main transcript	c.*875T>C		3_prime_UTR_variant, NMD_transcript_variant	37/39			ENSP00000506501

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152156

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

250682

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135460

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000472

AC:

AN:

1460892

Hom.:

Cov.:

AF XY:

0.0000509

AC XY:

AN XY:

726720

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:

0.0000603

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74316

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

AC:

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

Dec 19, 2023

The c.4936T>C (p.Y1646H) alteration is located in exon 36 (coding exon 35) of the DDX60 gene. This alteration results from a T to C substitution at nucleotide position 4936, causing the tyrosine (Y) at amino acid position 1646 to be replaced by a histidine (H). 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

Pathogenic

0.58

BayesDel_addAF

Benign

0.0090

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.89

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.73

MetaSVM

Benign

-0.57

MutationAssessor

Pathogenic

2.9

MutationTaster

Benign

0.95

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-3.9

REVEL

Uncertain

0.41

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.51

MutPred

0.76

Loss of stability (P = 0.0076);

MVP

0.47

MPC

0.74

ClinPred

0.96

GERP RS

4.9

Varity_R

0.78

gMVP

0.68

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