17-18184290-C-A

Variant names:

• chr17-18184290-C-A
• rs2047121417
• NM_017758.4:c.47C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_017758.4(ALKBH5):​c.47C>A​(p.Ser16Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ALKBH5 NM_017758.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.97
• Publications: 0 publications found

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]

ENSG00000266677 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017758.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALKBH5	NM_017758.4	MANE Select	c.47C>A	p.Ser16Tyr	missense	Exon 1 of 4	NP_060228.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALKBH5	ENST00000399138.5	TSL:2 MANE Select	c.47C>A	p.Ser16Tyr	missense	Exon 1 of 4	ENSP00000382091.4	Q6P6C2-2
	ALKBH5	ENST00000541285.1	TSL:1	c.-254+1025C>A		intron	N/A	ENSP00000468116.1	K7ER58
	ENSG00000266677	ENST00000583062.2	TSL:1	n.395+107G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1375594 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 678970

African (AFR) AF: 0.00 AC: 0 AN: 28802

American (AMR) AF: 0.00 AC: 0 AN: 32604

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24500

East Asian (EAS) AF: 0.00 AC: 0 AN: 33722

South Asian (SAS) AF: 0.00 AC: 0 AN: 77374

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44490

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4728

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1072448

Other (OTH) AF: 0.00 AC: 0 AN: 56926

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.054	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	T
M_CAP	Pathogenic	0.73	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	1.5	L
PhyloP100		5.0
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.30
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0070	D
Vest4		0.52
MutPred		0.22		Loss of methylation at K13 (P = 0.082)
MVP		0.30
MPC		3.2
ClinPred		0.98	D
GERP RS		4.5
PromoterAI		0.0067	Neutral
Varity_R		0.79
gMVP		0.58

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

Other links and lift over

dbSNP: rs2047121417; hg19: chr17-18087604;