Variant 9-137307162-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_017820.5(EXD3):c.2419G>A(p.Asp807Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000528 in 1,589,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

EXD3
NM_017820.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.119

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0166789).

BP6

Variant 9-137307162-C-T is Benign according to our data. Variant chr9-137307162-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2342376.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXD3	NM_017820.5 linkuse as main transcript	c.2419G>A	p.Asp807Asn	missense_variant	22/22	ENST00000340951.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXD3	ENST00000340951.9 linkuse as main transcript	c.2419G>A	p.Asp807Asn	missense_variant	22/22	1	NM_017820.5	P1	Q8N9H8-1
EXD3	ENST00000491734.6 linkuse as main transcript	c.*1487G>A		3_prime_UTR_variant, NMD_transcript_variant	15/15	1
EXD3	ENST00000487745.5 linkuse as main transcript	n.1747G>A		non_coding_transcript_exon_variant	12/12	2

Frequencies

GnomAD3 genomes

AF:

0.000283

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000654

AC:

AN:

198826

Hom.:

AF XY:

0.0000460

AC XY:

AN XY:

108694

show subpopulations

Gnomad AFR exome

AF:

0.000635

Gnomad AMR exome

AF:

0.000103

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000744

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000117

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000292

AC:

AN:

1437604

Hom.:

Cov.:

AF XY:

0.0000196

AC XY:

AN XY:

713350

show subpopulations

Gnomad4 AFR exome

AF:

0.000668

Gnomad4 AMR exome

AF:

0.0000741

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000261

Gnomad4 SAS exome

AF:

0.0000479

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000726

Gnomad4 OTH exome

AF:

0.0000673

GnomAD4 genome

AF:

0.000276

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000987

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.0000413

Hom.:

Bravo

AF:

0.000238

ESP6500AA

AF:

0.000753

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000839

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 23, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.74

DANN

Benign

0.86

DEOGEN2

Benign

0.00051

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0039

LIST_S2

Benign

0.40

M_CAP

Benign

0.014

MetaRNN

Benign

0.017

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.2

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.46

PROVEAN

Benign

0.64

REVEL

Benign

0.061

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.032

MVP

0.072

MPC

0.052

ClinPred

0.0047

GERP RS

2.0

Varity_R

0.036

gMVP

0.12

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