NM_001012967.3:c.2980-2527G>T

Variant names:

• chr4-168409233-C-A
• rs17612333
• NM_001012967.3:c.2980-2527G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001012967.3(DDX60L):​c.2980-2527G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,124 control chromosomes in the GnomAD database, including 1,250 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (1250 hom., cov: 32)
• Consequence: DDX60L NM_001012967.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 7 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX60L	NM_001012967.3	c.2980-2527G>T		intron_variant	Intron 22 of 37	ENST00000682922.1	NP_001012985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX60L	ENST00000682922.1	c.2980-2527G>T		intron_variant	Intron 22 of 37		NM_001012967.3	ENSP00000507872.1
DDX60L	ENST00000511577.5	c.2980-2527G>T		intron_variant	Intron 22 of 37	5		ENSP00000422423.1
DDX60L	ENST00000505890.5	c.2980-2527G>T		intron_variant	Intron 22 of 29	2		ENSP00000422202.1
DDX60L	ENST00000505863.1	c.2068-2527G>T		intron_variant	Intron 15 of 19	2		ENSP00000421026.1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16643 AN: 152006 Hom.: 1250 Cov.: 32

Gnomad AFR AF: 0.0224

Gnomad AMI AF: 0.0901

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.0919

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.103

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.109 AC: 16637 AN: 152124 Hom.: 1250 Cov.: 32 AF XY: 0.115 AC XY: 8578 AN XY: 74362

African (AFR) AF: 0.0223 AC: 927 AN: 41536

American (AMR) AF: 0.150 AC: 2288 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0919 AC: 319 AN: 3470

East Asian (EAS) AF: 0.138 AC: 713 AN: 5162

South Asian (SAS) AF: 0.132 AC: 633 AN: 4810

European-Finnish (FIN) AF: 0.232 AC: 2452 AN: 10564

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8997 AN: 67988

Other (OTH) AF: 0.102 AC: 214 AN: 2106

Alfa AF: 0.0886 Hom.: 167

Bravo AF: 0.101

Asia WGS AF: 0.127 AC: 439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.71
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs17612333; hg19: chr4-169330384;