rs6494562

chr15-66308291-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001143688.3(DIS3L):c.423-418C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0603 in 152,156 control chromosomes in the GnomAD database, including 366 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 0.060 (366 hom., cov: 31)
• Consequence: DIS3L NM_001143688.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160

Genes affected

DIS3L (HGNC:28698): (DIS3 like exosome 3'-5' exoribonuclease) The cytoplasmic RNA exosome complex degrades unstable mRNAs and is involved in the regular turnover of other mRNAs. The protein encoded by this gene contains 3'-5' exoribonuclease activity and is a catalytic component of this complex. [provided by RefSeq, May 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DIS3L	NM_001143688.3	c.423-418C>T		intron_variant		ENST00000319212.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DIS3L	ENST00000319212.9	c.423-418C>T		intron_variant		5	NM_001143688.3	P1

Frequencies

GnomAD3 genomes AF: 0.0603 AC: 9169 AN: 152038 Hom.: 365 Cov.: 31

Gnomad AFR AF: 0.0348

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.0461

Gnomad ASJ AF: 0.0937

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0301

Gnomad FIN AF: 0.0802

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0800

Gnomad OTH AF: 0.0670

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

GnomAD4 genome AF: 0.0603 AC: 9170 AN: 152156 Hom.: 366 Cov.: 31 AF XY: 0.0602 AC XY: 4476 AN XY: 74390

Gnomad4 AFR AF: 0.0348

Gnomad4 AMR AF: 0.0459

Gnomad4 ASJ AF: 0.0937

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0308

Gnomad4 FIN AF: 0.0802

Gnomad4 NFE AF: 0.0800

Gnomad4 OTH AF: 0.0664

Alfa AF: 0.0747 Hom.: 221

Bravo AF: 0.0566

Asia WGS AF: 0.0210 AC: 74 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	8.0
Dann	Benign	0.65

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

Other links and lift over

dbSNP: rs6494562; hg19: chr15-66600629;