rs2047282751

Variant names:

• chr17-18208389-G-A
• NM_017758.4:c.1178G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-18208389-G-A
• chr17-18208389-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017758.4(ALKBH5):​c.1178G>A​(p.Arg393Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ALKBH5 NM_017758.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.14

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34812194).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALKBH5	NM_017758.4	c.1178G>A	p.Arg393Gln	missense_variant	Exon 4 of 4	ENST00000399138.5	NP_060228.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALKBH5	ENST00000399138.5	c.1178G>A	p.Arg393Gln	missense_variant	Exon 4 of 4	2	NM_017758.4	ENSP00000382091.4
ALKBH5	ENST00000541285.1	c.155G>A	p.Arg52Gln	missense_variant	Exon 4 of 4	1		ENSP00000468116.1
ALKBH5	ENST00000490106.1	n.581G>A		non_coding_transcript_exon_variant	Exon 2 of 2	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460306 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726392

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: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.13	T;T
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	1.0	.;L
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-0.67	.;N
REVEL	Benign	0.25
Sift	Pathogenic	0.0	.;D
Sift4G	Pathogenic	0.0	D;D
Vest4		0.63
MutPred		0.22		.;Gain of relative solvent accessibility (P = 0.1571);
MVP		0.29
MPC		1.2
ClinPred		0.81	D
GERP RS		5.9
Varity_R		0.24
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-18111703; COSMIC: COSV104707065;