rs3759785

chr15-66333132-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001143688.3(DIS3L):c.2985G>A(p.Glu995=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0248 in 1,613,576 control chromosomes in the GnomAD database, including 925 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 0.023 (91 hom., cov: 31)
  • Exomes 𝑓: 0.025 (834 hom.)
• Consequence: DIS3L NM_001143688.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP7: Synonymous conserved (PhyloP=-1.75 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DIS3L	NM_001143688.3	c.2985G>A	p.Glu995=	synonymous_variant	17/17	ENST00000319212.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DIS3L	ENST00000319212.9	c.2985G>A	p.Glu995=	synonymous_variant	17/17	5	NM_001143688.3	P1
DIS3L	ENST00000319194.9	c.2736G>A	p.Glu912=	synonymous_variant	17/17	1
DIS3L	ENST00000530537.1	c.*2495G>A		3_prime_UTR_variant, NMD_transcript_variant	16/16	1

Frequencies

GnomAD3 genomes AF: 0.0233 AC: 3535 AN: 152040 Hom.: 91 Cov.: 31

Gnomad AFR AF: 0.00630

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0655

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.0715

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.0354

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0197

Gnomad OTH AF: 0.0230

GnomAD3 exomes AF: 0.0342 AC: 8573 AN: 250922 Hom.: 316 AF XY: 0.0304 AC XY: 4129 AN XY: 135666

Gnomad AFR exome AF: 0.00647

Gnomad AMR exome AF: 0.104

Gnomad ASJ exome AF: 0.0248

Gnomad EAS exome AF: 0.0714

Gnomad SAS exome AF: 0.00990

Gnomad FIN exome AF: 0.0337

Gnomad NFE exome AF: 0.0185

Gnomad OTH exome AF: 0.0286

GnomAD4 exome AF: 0.0250 AC: 36464 AN: 1461418 Hom.: 834 Cov.: 32 AF XY: 0.0240 AC XY: 17432 AN XY: 727010

Gnomad4 AFR exome AF: 0.00487

Gnomad4 AMR exome AF: 0.100

Gnomad4 ASJ exome AF: 0.0250

Gnomad4 EAS exome AF: 0.104

Gnomad4 SAS exome AF: 0.0102

Gnomad4 FIN exome AF: 0.0330

Gnomad4 NFE exome AF: 0.0206

Gnomad4 OTH exome AF: 0.0251

GnomAD4 genome AF: 0.0232 AC: 3534 AN: 152158 Hom.: 91 Cov.: 31 AF XY: 0.0249 AC XY: 1854 AN XY: 74382

Gnomad4 AFR AF: 0.00629

Gnomad4 AMR AF: 0.0655

Gnomad4 ASJ AF: 0.0256

Gnomad4 EAS AF: 0.0716

Gnomad4 SAS AF: 0.0110

Gnomad4 FIN AF: 0.0354

Gnomad4 NFE AF: 0.0197

Gnomad4 OTH AF: 0.0223

Alfa AF: 0.0224 Hom.: 87

Bravo AF: 0.0264

Asia WGS AF: 0.0360 AC: 125 AN: 3478

EpiCase AF: 0.0172

EpiControl AF: 0.0162

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.14
Dann	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3759785; hg19: chr15-66625470; COSMIC: COSV56019627; COSMIC: COSV56019627;