chr19-1819051-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_020695.4(REXO1):c.2731C>T(p.Arg911Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000187 in 1,602,804 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 0.000053 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000015 ( 0 hom. )
Consequence
REXO1
NM_020695.4 missense
NM_020695.4 missense
Scores
7
12
Clinical Significance
Conservation
PhyloP100: 1.90
Genes affected
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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=0.1515643).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
REXO1 | NM_020695.4 | c.2731C>T | p.Arg911Cys | missense_variant | 8/16 | ENST00000170168.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
REXO1 | ENST00000170168.9 | c.2731C>T | p.Arg911Cys | missense_variant | 8/16 | 1 | NM_020695.4 | P2 | |
REXO1 | ENST00000643515.1 | c.658C>T | p.Arg220Cys | missense_variant | 4/12 | A2 | |||
REXO1 | ENST00000590936.5 | c.112C>T | p.Arg38Cys | missense_variant, NMD_transcript_variant | 2/10 | 5 | |||
REXO1 | ENST00000586343.2 | c.*316C>T | 3_prime_UTR_variant, NMD_transcript_variant | 4/6 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152190Hom.: 0 Cov.: 34
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000288 AC: 7AN: 243094Hom.: 0 AF XY: 0.00000759 AC XY: 1AN XY: 131826
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GnomAD4 exome AF: 0.0000152 AC: 22AN: 1450496Hom.: 0 Cov.: 33 AF XY: 0.00000833 AC XY: 6AN XY: 720316
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GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152308Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74484
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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 submitter | clinical testing | Ambry Genetics | May 03, 2023 | The c.2731C>T (p.R911C) alteration is located in exon 8 (coding exon 8) of the REXO1 gene. This alteration results from a C to T substitution at nucleotide position 2731, causing the arginine (R) at amino acid position 911 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.
REVEL
Benign
Sift
Uncertain
D;.
Sift4G
Uncertain
D;.
Polyphen
P;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at