chr15-34897560-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP2PP3BS2
The NM_014691.3(AQR):c.2389C>T(p.Arg797Cys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000254 in 1,613,860 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000025 ( 1 hom. )
Consequence
AQR
NM_014691.3 missense, splice_region
NM_014691.3 missense, splice_region
Scores
9
9
1
Splicing: ADA: 0.9947
2
Clinical Significance
Conservation
PhyloP100: 6.28
Genes affected
AQR (HGNC:29513): (aquarius intron-binding spliceosomal factor) Enables 3'-5' RNA helicase activity and single-stranded RNA binding activity. Involved in mRNA splicing, via spliceosome. Located in nucleoplasm. Part of U2-type catalytic step 2 spliceosome. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, AQR
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.766
BS2
?
High AC in GnomAdExome at 14 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AQR | NM_014691.3 | c.2389C>T | p.Arg797Cys | missense_variant, splice_region_variant | 21/35 | ENST00000156471.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AQR | ENST00000156471.10 | c.2389C>T | p.Arg797Cys | missense_variant, splice_region_variant | 21/35 | 1 | NM_014691.3 | P1 | |
AQR | ENST00000543879.6 | c.*474C>T | splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant | 21/34 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152136Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000561 AC: 14AN: 249366Hom.: 0 AF XY: 0.0000887 AC XY: 12AN XY: 135290
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GnomAD4 exome AF: 0.0000253 AC: 37AN: 1461606Hom.: 1 Cov.: 31 AF XY: 0.0000385 AC XY: 28AN XY: 727112
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152254Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74446
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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 | Jul 20, 2022 | The c.2389C>T (p.R797C) alteration is located in exon 21 (coding exon 21) of the AQR gene. This alteration results from a C to T substitution at nucleotide position 2389, causing the arginine (R) at amino acid position 797 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
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Uncertain
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at