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GeneBe

19-1816538-C-T

Variant summary

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

The NM_020695.4(REXO1):c.3349G>A(p.Asp1117Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000498 in 1,606,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

REXO1
NM_020695.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.53
Variant links:
Genes affected
REXO1 (HGNC:24616): (RNA exonuclease 1 homolog) Predicted to enable exonuclease activity. Predicted to be involved in nucleic acid phosphodiester bond hydrolysis. Located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

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=0.076382786).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
REXO1NM_020695.4 linkuse as main transcriptc.3349G>A p.Asp1117Asn missense_variant 14/16 ENST00000170168.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
REXO1ENST00000170168.9 linkuse as main transcriptc.3349G>A p.Asp1117Asn missense_variant 14/161 NM_020695.4 P2
REXO1ENST00000643515.1 linkuse as main transcriptc.1276G>A p.Asp426Asn missense_variant 10/12 A2
REXO1ENST00000586291.1 linkuse as main transcriptn.100G>A non_coding_transcript_exon_variant 2/23
REXO1ENST00000590936.5 linkuse as main transcriptc.*373G>A 3_prime_UTR_variant, NMD_transcript_variant 8/105

Frequencies

GnomAD3 genomes
AF:
0.00000670
AC:
1
AN:
149246
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000148
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
249214
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135428
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000893
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000480
AC:
7
AN:
1457638
Hom.:
0
Cov.:
39
AF XY:
0.00000414
AC XY:
3
AN XY:
724944
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000451
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000670
AC:
1
AN:
149246
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
72652
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000148
Gnomad4 OTH
AF:
0.00

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 submitterclinical testingAmbry GeneticsDec 07, 2021The c.3349G>A (p.D1117N) alteration is located in exon 14 (coding exon 14) of the REXO1 gene. This alteration results from a G to A substitution at nucleotide position 3349, causing the aspartic acid (D) at amino acid position 1117 to be replaced by an asparagine (N). 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
0.080
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.74
Cadd
Benign
13
Dann
Benign
0.67
DEOGEN2
Benign
0.016
T;.
Eigen
Benign
-0.87
Eigen_PC
Benign
-0.70
FATHMM_MKL
Benign
0.65
D
LIST_S2
Benign
0.24
T;T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.076
T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
-0.73
N;.
MutationTaster
Benign
0.57
D
PrimateAI
Benign
0.42
T
PROVEAN
Benign
1.3
N;.
REVEL
Benign
0.14
Sift
Benign
0.97
T;.
Sift4G
Benign
1.0
T;.
Polyphen
0.093
B;.
Vest4
0.17
MutPred
0.30
Gain of catalytic residue at D1117 (P = 0.1032);.;
MVP
0.18
MPC
0.20
ClinPred
0.098
T
GERP RS
3.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.069
gMVP
0.52

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs1418399899; hg19: chr19-1816537; API