9-133412830-G-C

Variant names:

• chr9-133412830-G-C
• rs1839299409
• NM_020385.4:c.664C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020385.4(REXO4):​c.664C>G​(p.Gln222Glu) 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. 14/23 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: 32)
• Consequence: REXO4 NM_020385.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.51

Genes affected

REXO4 (HGNC:12820): (REX4 homolog, 3'-5' exonuclease) Enables DNA binding activity and nuclease activity. Involved in DNA catabolic process, endonucleolytic; DNA catabolic process, exonucleolytic; and DNA repair. Located in nuclear speck and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REXO4	NM_020385.4	c.664C>G	p.Gln222Glu	missense_variant	Exon 3 of 8	ENST00000371942.8	NP_065118.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REXO4	ENST00000371942.8	c.664C>G	p.Gln222Glu	missense_variant	Exon 3 of 8	1	NM_020385.4	ENSP00000361010.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	18
DANN	Benign	0.92
DEOGEN2	Benign	0.018	T;.
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.55	T;T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.050	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	N;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.039
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.062	B;.
Vest4		0.12
MutPred		0.31		Gain of sheet (P = 0.0266);.;
MVP		0.27
MPC		0.25
ClinPred		0.10	T
GERP RS		3.1
Varity_R		0.053
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.45		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.45		Position offset: 3

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

Publications

LitVar

Other links and lift over

dbSNP: rs1839299409; hg19: chr9-136277950;