dbSNP rs199671547: EXD3:p.Val738Phe (chr9-137309673-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_017820.5(EXD3):c.2212G>T(p.Val738Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000501 in 1,558,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

EXD3
NM_017820.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.202

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.035263926).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017820.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXD3	NM_017820.5	MANE Select	c.2212G>T	p.Val738Phe	missense	Exon 20 of 22	NP_060290.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EXD3	ENST00000340951.9	TSL:1 MANE Select	c.2212G>T	p.Val738Phe	missense	Exon 20 of 22	ENSP00000340474.4	Q8N9H8-1
EXD3	ENST00000491734.6	TSL:1	n.*1319G>T		non_coding_transcript_exon	Exon 14 of 15	ENSP00000435830.1	E9PSB6
EXD3	ENST00000491734.6	TSL:1	n.*1319G>T		3_prime_UTR	Exon 14 of 15	ENSP00000435830.1	E9PSB6

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000917

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000658

AC:

AN:

167124

AF XY:

0.0000901

show subpopulations

Gnomad AFR exome

AF:

0.00124

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.0000256

AC:

AN:

1406010

Hom.:

Cov.:

AF XY:

0.0000202

AC XY:

AN XY:

694274

show subpopulations

African (AFR)

AF:

0.00100

AC:

AN:

31956

American (AMR)

AF:

0.00

AC:

AN:

36676

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25336

East Asian (EAS)

AF:

0.00

AC:

AN:

36396

South Asian (SAS)

AF:

0.00

AC:

AN:

79718

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48712

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1083174

Other (OTH)

AF:

0.0000686

AC:

AN:

58348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000276

AC:

AN:

152322

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.000914

AC:

AN:

41566

American (AMR)

AF:

0.0000653

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68034

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000231

Hom.:

Bravo

AF:

0.000314

ESP6500AA

AF:

0.000515

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000790

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.061

Eigen

Benign

0.043

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.66

M_CAP

Benign

0.067

MetaRNN

Benign

0.035

MetaSVM

Benign

-0.55

MutationAssessor

Pathogenic

3.0

PhyloP100

-0.20

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-2.9

REVEL

Uncertain

0.35

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.0090

Polyphen

0.99

Vest4

0.43

MVP

0.47

MPC

0.39

ClinPred

0.38

GERP RS

1.4

Varity_R

0.22

gMVP

0.82

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over