17-18206880-A-G

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

Scores

1
9
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.58
Variant links:
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]

Genome browser will be placed here

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
ALKBH5NM_017758.4 linkuse as main transcriptc.917A>G p.Tyr306Cys missense_variant 3/4 ENST00000399138.5 NP_060228.3 Q6P6C2-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ALKBH5ENST00000541285.1 linkuse as main transcriptc.-107A>G 5_prime_UTR_premature_start_codon_gain_variant 3/41 ENSP00000468116.1 K7ER58
ALKBH5ENST00000399138.5 linkuse as main transcriptc.917A>G p.Tyr306Cys missense_variant 3/42 NM_017758.4 ENSP00000382091.4 Q6P6C2-2
ALKBH5ENST00000541285.1 linkuse as main transcriptc.-107A>G 5_prime_UTR_variant 3/41 ENSP00000468116.1 K7ER58
ALKBH5ENST00000490106.1 linkuse as main transcriptn.320A>G non_coding_transcript_exon_variant 1/21

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000801
AC:
2
AN:
249558
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135392
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000356
AC:
52
AN:
1461890
Hom.:
0
Cov.:
30
AF XY:
0.0000330
AC XY:
24
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000414
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000624
Hom.:
0
Bravo
AF:
0.00000756
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000242
AC:
2
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 submitterclinical testingAmbry GeneticsMar 16, 2022The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.073
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.040
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.061
T
Eigen
Uncertain
0.52
Eigen_PC
Uncertain
0.56
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.88
D
M_CAP
Benign
0.0077
T
MetaRNN
Uncertain
0.62
D
MetaSVM
Benign
-0.61
T
MutationAssessor
Benign
1.7
L
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-2.0
N
REVEL
Benign
0.21
Sift
Uncertain
0.0060
D
Sift4G
Benign
0.17
T
Vest4
0.83
MVP
0.27
MPC
1.2
ClinPred
0.80
D
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.17
gMVP
0.24

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs377225153; hg19: chr17-18110194; API