9-137349428-G-C

Variant names:

• chr9-137349428-G-C
• rs35097575
• NM_017820.5:c.1598C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017820.5(EXD3):​c.1598C>G​(p.Thr533Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T533M) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EXD3 NM_017820.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96
• Publications: 10 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07177454).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXD3	NM_017820.5	MANE Select	c.1598C>G	p.Thr533Arg	missense	Exon 15 of 22	NP_060290.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXD3	ENST00000340951.9	TSL:1 MANE Select	c.1598C>G	p.Thr533Arg	missense	Exon 15 of 22	ENSP00000340474.4
	EXD3	ENST00000491734.6	TSL:1	n.*792C>G		non_coding_transcript_exon	Exon 9 of 15	ENSP00000435830.1
	EXD3	ENST00000491734.6	TSL:1	n.*792C>G		3_prime_UTR	Exon 9 of 15	ENSP00000435830.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 233

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	12
DANN	Benign	0.85
DEOGEN2	Benign	0.0074	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.73	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.89	L
PhyloP100		2.0
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.031
Sift	Benign	0.21	T
Sift4G	Benign	0.25	T
Polyphen		0.031	B
Vest4		0.12
MutPred		0.38		Gain of MoRF binding (P = 0.0441)
MVP		0.18
MPC		0.060
ClinPred		0.081	T
GERP RS		0.65
Varity_R		0.14
gMVP		0.31
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs35097575; hg19: chr9-140243880;