rs3759785

Variant names:

• chr15-66333132-G-A
• rs3759785
• NM_001143688.3:c.2985G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001143688.3(DIS3L):​c.2985G>A​(p.Glu995Glu) 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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143688.3. 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
	DIS3L	NM_001143688.3	MANE Select	c.2985G>A	p.Glu995Glu	synonymous	Exon 17 of 17	NP_001137160.1
	DIS3L	NM_001323944.2		c.2934G>A	p.Glu978Glu	synonymous	Exon 17 of 17	NP_001310873.1
	DIS3L	NM_001323948.2		c.2805G>A	p.Glu935Glu	synonymous	Exon 16 of 16	NP_001310877.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIS3L	ENST00000319212.9	TSL:5 MANE Select	c.2985G>A	p.Glu995Glu	synonymous	Exon 17 of 17	ENSP00000321711.4
	DIS3L	ENST00000319194.9	TSL:1	c.2736G>A	p.Glu912Glu	synonymous	Exon 17 of 17	ENSP00000321583.5
	DIS3L	ENST00000530537.1	TSL:1	n.*2495G>A		non_coding_transcript_exon	Exon 16 of 16	ENSP00000432407.1

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

GnomAD2 exomes AF: 0.0342 AC: 8573 AN: 250922 AF XY: 0.0304

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 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

African (AFR) AF: 0.00487 AC: 163 AN: 33480

American (AMR) AF: 0.100 AC: 4475 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0250 AC: 653 AN: 26134

East Asian (EAS) AF: 0.104 AC: 4112 AN: 39690

South Asian (SAS) AF: 0.0102 AC: 882 AN: 86258

European-Finnish (FIN) AF: 0.0330 AC: 1749 AN: 52974

Middle Eastern (MID) AF: 0.00347 AC: 20 AN: 5768

European-Non Finnish (NFE) AF: 0.0206 AC: 22896 AN: 1112000

Other (OTH) AF: 0.0251 AC: 1514 AN: 60394

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

African (AFR) AF: 0.00629 AC: 261 AN: 41520

American (AMR) AF: 0.0655 AC: 999 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0256 AC: 89 AN: 3472

East Asian (EAS) AF: 0.0716 AC: 370 AN: 5166

South Asian (SAS) AF: 0.0110 AC: 53 AN: 4822

European-Finnish (FIN) AF: 0.0354 AC: 375 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0197 AC: 1338 AN: 68016

Other (OTH) AF: 0.0223 AC: 47 AN: 2108

Alfa AF: 0.0225 Hom.: 122

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.14
DANN	Benign	0.47
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3759785; hg19: chr15-66625470; COSMIC: COSV56019627; COSMIC: COSV56019627;