chr15-34862901-A-G
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The NM_014691.3(AQR):c.3995T>C(p.Ile1332Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,613,698 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000031 ( 1 hom. )
Consequence
AQR
NM_014691.3 missense
NM_014691.3 missense
Scores
8
9
2
Clinical Significance
Conservation
PhyloP100: 9.27
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 -3 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, AQR
BS2
?
High AC in GnomAd at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AQR | NM_014691.3 | c.3995T>C | p.Ile1332Thr | missense_variant | 33/35 | ENST00000156471.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AQR | ENST00000156471.10 | c.3995T>C | p.Ile1332Thr | missense_variant | 33/35 | 1 | NM_014691.3 | P1 | |
AQR | ENST00000559090.5 | n.2882T>C | non_coding_transcript_exon_variant | 2/4 | 1 | ||||
AQR | ENST00000559767.1 | n.324T>C | non_coding_transcript_exon_variant | 1/3 | 2 | ||||
AQR | ENST00000543879.6 | c.*2757T>C | 3_prime_UTR_variant, NMD_transcript_variant | 32/34 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152186Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000482 AC: 12AN: 249206Hom.: 1 AF XY: 0.0000740 AC XY: 10AN XY: 135204
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GnomAD4 exome AF: 0.0000308 AC: 45AN: 1461512Hom.: 1 Cov.: 31 AF XY: 0.0000413 AC XY: 30AN XY: 727064
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74338
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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 | Jan 30, 2024 | The c.3995T>C (p.I1332T) alteration is located in exon 33 (coding exon 33) of the AQR gene. This alteration results from a T to C substitution at nucleotide position 3995, causing the isoleucine (I) at amino acid position 1332 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D
MetaSVM
Pathogenic
D
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Gain of glycosylation at I1332 (P = 0.0104);
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