chr11-61356725-A-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_153611.6(CYB561A3):c.-12T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000039 in 1,613,354 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 0.00019 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )
Consequence
CYB561A3
NM_153611.6 5_prime_UTR
NM_153611.6 5_prime_UTR
Scores
2
13
Clinical Significance
Conservation
PhyloP100: -0.331
Genes affected
CYB561A3 (HGNC:23014): (cytochrome b561 family member A3) Predicted to enable transmembrane ascorbate ferrireductase activity. Predicted to be involved in cellular iron ion homeostasis. Located in nucleolus. [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.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.012295783).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYB561A3 | NM_153611.6 | c.-12T>C | 5_prime_UTR_variant | 3/7 | ENST00000294072.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYB561A3 | ENST00000294072.9 | c.-12T>C | 5_prime_UTR_variant | 3/7 | 1 | NM_153611.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000191 AC: 29AN: 152056Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000519 AC: 13AN: 250326Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135268
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GnomAD4 exome AF: 0.0000233 AC: 34AN: 1461180Hom.: 0 Cov.: 34 AF XY: 0.0000206 AC XY: 15AN XY: 726870
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GnomAD4 genome ? AF: 0.000191 AC: 29AN: 152174Hom.: 0 Cov.: 32 AF XY: 0.000229 AC XY: 17AN XY: 74396
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3478
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 31, 2022 | The c.40T>C (p.C14R) alteration is located in exon 4 (coding exon 2) of the CYB561A3 gene. This alteration results from a T to C substitution at nucleotide position 40, causing the cysteine (C) at amino acid position 14 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N;N;N;N
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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