chr15-34860074-G-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_014691.3(AQR):c.4111C>T(p.His1371Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000285 in 1,492,132 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 0.00018 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00030 ( 0 hom. )
Consequence
AQR
NM_014691.3 missense
NM_014691.3 missense
Scores
1
7
10
Clinical Significance
Conservation
PhyloP100: 7.70
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 -5 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, AQR
BP4
?
Computational evidence support a benign effect (MetaRNN=0.21951625).
BS2
?
High AC in GnomAd at 27 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AQR | NM_014691.3 | c.4111C>T | p.His1371Tyr | missense_variant | 34/35 | ENST00000156471.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AQR | ENST00000156471.10 | c.4111C>T | p.His1371Tyr | missense_variant | 34/35 | 1 | NM_014691.3 | P1 | |
AQR | ENST00000559090.5 | n.2998C>T | non_coding_transcript_exon_variant | 3/4 | 1 | ||||
AQR | ENST00000559767.1 | n.440C>T | non_coding_transcript_exon_variant | 2/3 | 2 | ||||
AQR | ENST00000543879.6 | c.*2873C>T | 3_prime_UTR_variant, NMD_transcript_variant | 33/34 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000177 AC: 27AN: 152156Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000140 AC: 31AN: 221380Hom.: 0 AF XY: 0.000165 AC XY: 20AN XY: 121058
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GnomAD4 exome AF: 0.000297 AC: 398AN: 1339858Hom.: 0 Cov.: 28 AF XY: 0.000305 AC XY: 201AN XY: 659052
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GnomAD4 genome ? AF: 0.000177 AC: 27AN: 152274Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10AN XY: 74458
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ExAC
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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 | Apr 25, 2022 | The c.4111C>T (p.H1371Y) alteration is located in exon 34 (coding exon 34) of the AQR gene. This alteration results from a C to T substitution at nucleotide position 4111, causing the histidine (H) at amino acid position 1371 to be replaced by a tyrosine (Y). 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
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
B
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