DIS3L p.Gly1030Glu

Variant names:

• chr15-66333236-G-A
• rs193920782
• NM_001143688.3:c.3089G>A
• DIS3L p.Gly1030Glu

Your query was ambiguous. Multiple possible variants found:

• chr15-66333236-G-A
• chr15-66333236-GA-AG

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001143688.3(DIS3L):​c.3089G>A​(p.Gly1030Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,876 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 (no stars).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DIS3L NM_001143688.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 6.65
• Publications: 1 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34532624).

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.3089G>A	p.Gly1030Glu	missense	Exon 17 of 17	NP_001137160.1	Q8TF46-1
	DIS3L	NM_001323944.2		c.3038G>A	p.Gly1013Glu	missense	Exon 17 of 17	NP_001310873.1
	DIS3L	NM_001323948.2		c.2909G>A	p.Gly970Glu	missense	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.3089G>A	p.Gly1030Glu	missense	Exon 17 of 17	ENSP00000321711.4	Q8TF46-1
	DIS3L	ENST00000319194.9	TSL:1	c.2840G>A	p.Gly947Glu	missense	Exon 17 of 17	ENSP00000321583.5	Q8TF46-4
	DIS3L	ENST00000530537.1	TSL:1	n.*2599G>A		non_coding_transcript_exon	Exon 16 of 16	ENSP00000432407.1	E9PKI7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461876 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727238

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0083	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		6.7
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.19
Sift	Benign	0.15	T
Sift4G	Benign	0.65	T
Varity_R		0.14
gMVP		0.38
Mutation Taster		=68/32	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs193920782;

hg19: chr15-66625574;

COSMIC: COSV56020240;

COSMIC: COSV56020240;