17-18206880-A-G
Position:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The ENST00000541285.1(ALKBH5):c.-107A>G variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.0000356 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000036 ( 0 hom. )
Consequence
ALKBH5
ENST00000541285.1 5_prime_UTR_premature_start_codon_gain
ENST00000541285.1 5_prime_UTR_premature_start_codon_gain
Scores
1
9
9
Clinical Significance
Conservation
PhyloP100: 4.58
Genes affected
ALKBH5 (HGNC:25996): (alkB homolog 5, RNA demethylase) Enables mRNA N6-methyladenosine dioxygenase activity. Involved in RNA metabolic process; mRNA export from nucleus; and response to hypoxia. Located in Golgi apparatus; cytosol; and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAdExome4 at 52 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ALKBH5 | NM_017758.4 | c.917A>G | p.Tyr306Cys | missense_variant | 3/4 | ENST00000399138.5 | NP_060228.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ALKBH5 | ENST00000541285.1 | c.-107A>G | 5_prime_UTR_premature_start_codon_gain_variant | 3/4 | 1 | ENSP00000468116.1 | ||||
ALKBH5 | ENST00000399138.5 | c.917A>G | p.Tyr306Cys | missense_variant | 3/4 | 2 | NM_017758.4 | ENSP00000382091.4 | ||
ALKBH5 | ENST00000541285.1 | c.-107A>G | 5_prime_UTR_variant | 3/4 | 1 | ENSP00000468116.1 | ||||
ALKBH5 | ENST00000490106.1 | n.320A>G | non_coding_transcript_exon_variant | 1/2 | 1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000801 AC: 2AN: 249558Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135392
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GnomAD4 exome AF: 0.0000356 AC: 52AN: 1461890Hom.: 0 Cov.: 30 AF XY: 0.0000330 AC XY: 24AN XY: 727244
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GnomAD4 genome Cov.: 32
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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 | Mar 16, 2022 | The c.917A>G (p.Y306C) alteration is located in exon 3 (coding exon 3) of the ALKBH5 gene. This alteration results from a A to G substitution at nucleotide position 917, causing the tyrosine (Y) at amino acid position 306 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
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Benign
L
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Benign
T
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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