NM_020385.4:c.1013A>G

Variant names:

• chr9-133408829-T-C
• rs782245774
• NM_020385.4:c.1013A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_020385.4(REXO4):​c.1013A>G​(p.Asp338Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000201 in 1,440,910 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: not found (cov: 31)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: REXO4 NM_020385.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.38
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10720253).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020385.4. 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
	REXO4	NM_020385.4	MANE Select	c.1013A>G	p.Asp338Gly	missense	Exon 6 of 8	NP_065118.2	Q9GZR2-1
	REXO4	NM_001279351.1		c.734A>G	p.Asp245Gly	missense	Exon 6 of 8	NP_001266280.1	Q9GZR2
	REXO4	NM_001279350.2		c.602A>G	p.Asp201Gly	missense	Exon 6 of 8	NP_001266279.1	B4E331

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REXO4	ENST00000371942.8	TSL:1 MANE Select	c.1013A>G	p.Asp338Gly	missense	Exon 6 of 8	ENSP00000361010.3	Q9GZR2-1
	REXO4	ENST00000903994.1		c.1037A>G	p.Asp346Gly	missense	Exon 6 of 8	ENSP00000574053.1
	REXO4	ENST00000903993.1		c.1031A>G	p.Asp344Gly	missense	Exon 6 of 8	ENSP00000574052.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000563 AC: 14 AN: 248476 AF XY: 0.0000297

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000419

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: 0.0000201 AC: 29 AN: 1440910 Hom.: 0 Cov.: 28 AF XY: 0.0000209 AC XY: 15 AN XY: 717968

African (AFR) AF: 0.00 AC: 0 AN: 32840

American (AMR) AF: 0.000343 AC: 15 AN: 43684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26002

East Asian (EAS) AF: 0.00 AC: 0 AN: 39538

South Asian (SAS) AF: 0.00 AC: 0 AN: 85444

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53310

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.0000128 AC: 14 AN: 1094676

Other (OTH) AF: 0.00 AC: 0 AN: 59698

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.0000824 AC: 10

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	23
DANN	Uncertain	0.97
DEOGEN2	Benign	0.0057	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.91	L
PhyloP100		5.4
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.15
Sift	Benign	0.22	T
Sift4G	Benign	0.47	T
Polyphen		0.0080	B
Vest4		0.33
MutPred		0.46		Loss of stability (P = 0.0238)
MVP		0.25
MPC		0.30
ClinPred		0.15	T
GERP RS		4.2
Varity_R		0.24
gMVP		0.67
Mutation Taster		=38/62	disease causing

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: rs782245774; hg19: chr9-136273953;