Variant 13-72761500-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_014953.5(DIS3):c.2533A>G(p.Ile845Val) variant causes a missense change. The variant allele was found at a frequency of 0.00152 in 1,585,140 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0084 ( 25 hom., cov: 32)

Exomes 𝑓: 0.00079 ( 15 hom. )

Consequence

DIS3
NM_014953.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.91

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0048285425).

BP6

Variant 13-72761500-T-C is Benign according to our data. Variant chr13-72761500-T-C is described in ClinVar as [Benign]. Clinvar id is 2443114.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00837 (1275/152318) while in subpopulation AFR AF= 0.0296 (1232/41564). AF 95% confidence interval is 0.0283. There are 25 homozygotes in gnomad4. There are 602 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIS3	NM_014953.5 linkuse as main transcript	c.2533A>G	p.Ile845Val	missense_variant	19/21	ENST00000377767.9	NP_055768.3	Q9Y2L1-1
DIS3	NM_001128226.3 linkuse as main transcript	c.2443A>G	p.Ile815Val	missense_variant	19/21		NP_001121698.1	Q9Y2L1-2
DIS3	NM_001322348.2 linkuse as main transcript	c.2164A>G	p.Ile722Val	missense_variant	18/20		NP_001309277.1
DIS3	NM_001322349.2 linkuse as main transcript	c.2047A>G	p.Ile683Val	missense_variant	20/22		NP_001309278.1	G3V1J5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIS3	ENST00000377767.9 linkuse as main transcript	c.2533A>G	p.Ile845Val	missense_variant	19/21	1	NM_014953.5	ENSP00000366997.4		Q9Y2L1-1

Frequencies

GnomAD3 genomes

AF:

0.00836

AC:

1273

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0297

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00209

AC:

472

AN:

225322

Hom.:

AF XY:

0.00138

AC XY:

169

AN XY:

122452

show subpopulations

Gnomad AFR exome

AF:

0.0284

Gnomad AMR exome

AF:

0.000919

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000187

Gnomad OTH exome

AF:

0.000744

GnomAD4 exome

AF:

0.000795

AC:

1139

AN:

1432822

Hom.:

Cov.:

AF XY:

0.000642

AC XY:

457

AN XY:

712170

show subpopulations

Gnomad4 AFR exome

AF:

0.0302

Gnomad4 AMR exome

AF:

0.00110

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000501

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000209

Gnomad4 OTH exome

AF:

0.00188

GnomAD4 genome

AF:

0.00837

AC:

1275

AN:

152318

Hom.:

Cov.:

AF XY:

0.00808

AC XY:

602

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0296

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00108

Hom.:

Bravo

AF:

0.00929

ESP6500AA

AF:

0.0279

AC:

123

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00255

AC:

310

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 19, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0039

T;.;T

Eigen

Benign

-0.095

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.81

T;T;T

MetaRNN

Benign

0.0048

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.46

N;.;.

PrimateAI

Benign

0.43

PROVEAN

Benign

0.27

N;N;N

REVEL

Benign

0.059

Sift

Benign

0.95

T;T;T

Sift4G

Benign

0.73

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.14

MVP

0.30

MPC

0.11

ClinPred

0.016

GERP RS

5.9

Varity_R

0.041

gMVP

0.21

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