rs193920782

Positions:

• chr15-66333236-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIS3L	NM_001143688.3	c.3089G>A	p.Gly1030Glu	missense_variant	17/17	ENST00000319212.9	NP_001137160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIS3L	ENST00000319212.9	c.3089G>A	p.Gly1030Glu	missense_variant	17/17	5	NM_001143688.3	ENSP00000321711.4
DIS3L	ENST00000319194.9	c.2840G>A	p.Gly947Glu	missense_variant	17/17	1		ENSP00000321583.5
DIS3L	ENST00000530537.1	n.*2599G>A		non_coding_transcript_exon_variant	16/16	1		ENSP00000432407.1
DIS3L	ENST00000530537.1	n.*2599G>A		3_prime_UTR_variant	16/16	1		ENSP00000432407.1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

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;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.2	.;M
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.19
Sift	Benign	0.15	T;T
Sift4G	Benign	0.65	T;T
Polyphen		0.84	.;P
Vest4		0.65
MutPred		0.26		.;Gain of solvent accessibility (P = 0.0281);
MVP		0.59
MPC		0.71
ClinPred		0.92	D
GERP RS		5.8
Varity_R		0.14
gMVP		0.38

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: rs193920782; hg19: chr15-66625574; COSMIC: COSV56020240; COSMIC: COSV56020240;