Variant 9-137307640-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017820.5(EXD3):c.2285A>G(p.Glu762Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000185 in 1,457,496 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

EXD3
NM_017820.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00700

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:

EXD3 (HGNC:):

EXD3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.047812372).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXD3	NM_017820.5 linkuse as main transcript	c.2285A>G	p.Glu762Gly	missense_variant	21/22	ENST00000340951.9	NP_060290.3	Q8N9H8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
EXD3	ENST00000340951.9 linkuse as main transcript	c.2285A>G	p.Glu762Gly	missense_variant	21/22	1	NM_017820.5	ENSP00000340474.4	Q8N9H8-1
EXD3	ENST00000491734.6 linkuse as main transcript	n.*1386-377A>G		intron_variant		1		ENSP00000435830.1	E9PSB6
EXD3	ENST00000487745.5 linkuse as main transcript	n.1613A>G		non_coding_transcript_exon_variant	11/12	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000409

AC:

AN:

244560

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133554

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1457496

Hom.:

Cov.:

AF XY:

0.0000221

AC XY:

AN XY:

725204

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.0000234

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 02, 2024

The c.2285A>G (p.E762G) alteration is located in exon 21 (coding exon 20) of the EXD3 gene. This alteration results from a A to G substitution at nucleotide position 2285, causing the glutamic acid (E) at amino acid position 762 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.0073

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.32

M_CAP

Benign

0.0062

MetaRNN

Benign

0.048

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.5

REVEL

Benign

0.017

Sift

Benign

0.14

Sift4G

Uncertain

0.022

Polyphen

0.18

Vest4

0.15

MutPred

0.30

Loss of helix (P = 0.0167);

MVP

0.14

MPC

0.060

ClinPred

0.041

GERP RS

1.2

Varity_R

0.085

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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