NM_001012967.3:c.4539C>G

Variant names:

• chr4-168375471-G-C
• rs766033629
• NM_001012967.3:c.4539C>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001012967.3(DDX60L):​c.4539C>G​(p.Asn1513Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,612,894 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 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: DDX60L NM_001012967.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.63
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.28059107).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012967.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX60L	NM_001012967.3	MANE Select	c.4539C>G	p.Asn1513Lys	missense	Exon 34 of 38	NP_001012985.2	Q5H9U9-1
	DDX60L	NM_001345927.2		c.4542C>G	p.Asn1514Lys	missense	Exon 34 of 38	NP_001332856.1
	DDX60L	NM_001378072.1		c.4542C>G	p.Asn1514Lys	missense	Exon 35 of 39	NP_001365001.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX60L	ENST00000682922.1	MANE Select	c.4539C>G	p.Asn1513Lys	missense	Exon 34 of 38	ENSP00000507872.1	Q5H9U9-1
	DDX60L	ENST00000854594.1		c.4542C>G	p.Asn1514Lys	missense	Exon 34 of 38	ENSP00000524653.1
	DDX60L	ENST00000511577.5	TSL:5	c.4539C>G	p.Asn1513Lys	missense	Exon 34 of 38	ENSP00000422423.1	Q5H9U9-1

Frequencies

GnomAD3 genomes AF: 0.000138 AC: 21 AN: 152150 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00138

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000113 AC: 28 AN: 247402 AF XY: 0.0000894

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000789

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000167

GnomAD4 exome AF: 0.0000233 AC: 34 AN: 1460744 Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14 AN XY: 726578

African (AFR) AF: 0.00 AC: 0 AN: 33432

American (AMR) AF: 0.000718 AC: 32 AN: 44576

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39650

South Asian (SAS) AF: 0.00 AC: 0 AN: 86086

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111454

Other (OTH) AF: 0.0000331 AC: 2 AN: 60336

GnomAD4 genome AF: 0.000138 AC: 21 AN: 152150 Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14 AN XY: 74342

African (AFR) AF: 0.00 AC: 0 AN: 41420

American (AMR) AF: 0.00138 AC: 21 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000174

ExAC AF: 0.0000331 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	21
DANN	Uncertain	0.99
Eigen	Benign	0.039
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.50	N
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.98	T
PhyloP100		1.6
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.51
MutPred		0.70		Gain of ubiquitination at N1513 (P = 0.0369)
MVP		0.15
MPC		0.20
ClinPred		0.39	T
GERP RS		0.089
gMVP		0.37
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs766033629; hg19: chr4-169296622;