Variant chr13-72759797-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM4BP6_Very_StrongBS2

The NM_014953.5(DIS3):c.2875T>C(p.Ter959Glnext*?) variant causes a stop lost change. The variant allele was found at a frequency of 0.00261 in 1,611,450 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 11 hom. )

Consequence

DIS3
NM_014953.5 stop_lost

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.27

Variant links:

Genes affected

DIS3 (HGNC:20604): (DIS3 homolog, exosome endoribonuclease and 3'-5' exoribonuclease) Enables 3'-5'-exoribonuclease activity; endonuclease activity; and guanyl-nucleotide exchange factor activity. Involved in CUT catabolic process and rRNA catabolic process. Located in cytosol and nucleoplasm. Part of nuclear exosome (RNase complex). [provided by Alliance of Genome Resources, Apr 2022]

DIS3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

PM4

Stoplost variant in NM_014953.5 Downstream stopcodon found after 27 codons.

BP6

Variant 13-72759797-A-G is Benign according to our data. Variant chr13-72759797-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1336735.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIS3	NM_014953.5 link	c.2875T>C	p.Ter959Glnext*?	stop_lost	21/21	ENST00000377767.9	NP_055768.3	Q9Y2L1-1
DIS3	NM_001128226.3 link	c.2785T>C	p.Ter929Glnext*?	stop_lost	21/21		NP_001121698.1	Q9Y2L1-2
DIS3	NM_001322348.2 link	c.2506T>C	p.Ter836Glnext*?	stop_lost	20/20		NP_001309277.1
DIS3	NM_001322349.2 link	c.2389T>C	p.Ter797Glnext*?	stop_lost	22/22		NP_001309278.1	G3V1J5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIS3	ENST00000377767.9 link	c.2875T>C	p.Ter959Glnext*?	stop_lost	21/21	1	NM_014953.5	ENSP00000366997.4		Q9Y2L1-1

Frequencies

GnomAD3 genomes

AF:

0.00162

AC:

247

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000604

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.000721

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00293

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00138

AC:

344

AN:

248818

Hom.:

AF XY:

0.00139

AC XY:

187

AN XY:

134434

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.000703

Gnomad ASJ exome

AF:

0.0000999

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000871

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00245

Gnomad OTH exome

AF:

0.00165

GnomAD4 exome

AF:

0.00271

AC:

3961

AN:

1459280

Hom.:

Cov.:

AF XY:

0.00260

AC XY:

1885

AN XY:

725862

show subpopulations

Gnomad4 AFR exome

AF:

0.000450

Gnomad4 AMR exome

AF:

0.000787

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00103

Gnomad4 FIN exome

AF:

0.000412

Gnomad4 NFE exome

AF:

0.00328

Gnomad4 OTH exome

AF:

0.00261

GnomAD4 genome

AF:

0.00162

AC:

247

AN:

152170

Hom.:

Cov.:

AF XY:

0.00125

AC XY:

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.000602

Gnomad4 AMR

AF:

0.000720

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00293

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00245

Hom.:

Bravo

AF:

0.00173

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00314

AC:

ExAC

AF:

0.00139

AC:

169

EpiCase

AF:

0.00218

EpiControl

AF:

0.00231

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Nov 12, 2021

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.89

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.85

FATHMM_MKL

Uncertain

0.95

Vest4

0.13

GERP RS

6.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over