Variant rs35097575 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017820.5(EXD3):c.1598C>T(p.Thr533Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0477 in 1,600,154 control chromosomes in the GnomAD database, including 2,088 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.037 ( 161 hom., cov: 32)

Exomes 𝑓: 0.049 ( 1927 hom. )

Consequence

EXD3
NM_017820.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.96

Variant links:

Genes affected

EXD3 (HGNC:26023): (exonuclease 3'-5' domain containing 3) Predicted to enable 3'-5' exonuclease activity. Predicted to be involved in nucleic acid phosphodiester bond hydrolysis. [provided by Alliance of Genome Resources, Apr 2022]

EXD3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020832121).

BP6

Variant 9-137349428-G-A is Benign according to our data. Variant chr9-137349428-G-A is described in ClinVar as [Benign]. Clinvar id is 402840.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXD3	NM_017820.5 linkuse as main transcript	c.1598C>T	p.Thr533Met	missense_variant	15/22	ENST00000340951.9	NP_060290.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXD3	ENST00000340951.9 linkuse as main transcript	c.1598C>T	p.Thr533Met	missense_variant	15/22	1	NM_017820.5	ENSP00000340474	P1	Q8N9H8-1

Frequencies

GnomAD3 genomes

AF:

0.0370

AC:

5625

AN:

152178

Hom.:

161

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00885

Gnomad AMI

AF:

0.120

Gnomad AMR

AF:

0.0248

Gnomad ASJ

AF:

0.0202

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0238

Gnomad FIN

AF:

0.0673

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0560

Gnomad OTH

AF:

0.0225

GnomAD3 exomes

AF:

0.0363

AC:

8331

AN:

229656

Hom.:

213

AF XY:

0.0380

AC XY:

4793

AN XY:

126180

show subpopulations

Gnomad AFR exome

AF:

0.00869

Gnomad AMR exome

AF:

0.0146

Gnomad ASJ exome

AF:

0.0195

Gnomad EAS exome

AF:

0.000340

Gnomad SAS exome

AF:

0.0296

Gnomad FIN exome

AF:

0.0653

Gnomad NFE exome

AF:

0.0516

Gnomad OTH exome

AF:

0.0367

GnomAD4 exome

AF:

0.0489

AC:

70751

AN:

1447858

Hom.:

1927

Cov.:

AF XY:

0.0488

AC XY:

35157

AN XY:

720032

show subpopulations

Gnomad4 AFR exome

AF:

0.00804

Gnomad4 AMR exome

AF:

0.0148

Gnomad4 ASJ exome

AF:

0.0201

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0311

Gnomad4 FIN exome

AF:

0.0652

Gnomad4 NFE exome

AF:

0.0549

Gnomad4 OTH exome

AF:

0.0440

GnomAD4 genome

AF:

0.0369

AC:

5624

AN:

152296

Hom.:

161

Cov.:

AF XY:

0.0372

AC XY:

2771

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00883

Gnomad4 AMR

AF:

0.0248

Gnomad4 ASJ

AF:

0.0202

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0236

Gnomad4 FIN

AF:

0.0673

Gnomad4 NFE

AF:

0.0560

Gnomad4 OTH

AF:

0.0222

Alfa

AF:

0.0470

Hom.:

189

Bravo

AF:

0.0311

TwinsUK

AF:

0.0520

AC:

193

ALSPAC

AF:

0.0493

AC:

190

ESP6500AA

AF:

0.0101

AC:

ESP6500EA

AF:

0.0500

AC:

422

ExAC

AF:

0.0358

AC:

4282

Asia WGS

AF:

0.00895

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.038

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.064

LIST_S2

Benign

0.81

MetaRNN

Benign

0.0021

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.10

Sift

Benign

0.091

Sift4G

Uncertain

0.018

Polyphen

0.90

Vest4

0.077

MPC

0.23

ClinPred

0.012

GERP RS

0.65

Varity_R

0.073

gMVP

0.21

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

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