Variant 9-137309637-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017820.5(EXD3):c.2248A>T(p.Ser750Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000425 in 1,410,564 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

EXD3
NM_017820.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.416

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16572797).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXD3	NM_017820.5 linkuse as main transcript	c.2248A>T	p.Ser750Cys	missense_variant	20/22	ENST00000340951.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXD3	ENST00000340951.9 linkuse as main transcript	c.2248A>T	p.Ser750Cys	missense_variant	20/22	1	NM_017820.5	P1	Q8N9H8-1
EXD3	ENST00000491734.6 linkuse as main transcript	c.*1355A>T		3_prime_UTR_variant, NMD_transcript_variant	14/15	1
EXD3	ENST00000487745.5 linkuse as main transcript	n.1576A>T		non_coding_transcript_exon_variant	10/12	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000229

AC:

AN:

174732

Hom.:

AF XY:

0.0000215

AC XY:

AN XY:

93190

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000323

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:

0.00000425

AC:

AN:

1410564

Hom.:

Cov.:

AF XY:

0.00000287

AC XY:

AN XY:

696930

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000163

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Apr 22, 2024

The c.2248A>T (p.S750C) alteration is located in exon 20 (coding exon 19) of the EXD3 gene. This alteration results from a A to T substitution at nucleotide position 2248, causing the serine (S) at amino acid position 750 to be replaced by a cysteine (C). 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

0.089

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0025

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.48

M_CAP

Benign

0.071

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.84

MutationAssessor

Benign

1.5

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-2.0

REVEL

Benign

0.082

Sift

Uncertain

0.023

Sift4G

Uncertain

0.058

Polyphen

0.98

Vest4

0.18

MutPred

0.49

Loss of disorder (P = 0.0377);

MVP

0.32

MPC

0.29

ClinPred

0.13

GERP RS

0.88

Varity_R

0.079

gMVP

0.48

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