rs777703982

Variant names:

• chr11-43892059-C-G
• NM_139178.4:c.389C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-43892059-C-G
• chr11-43892059-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_139178.4(ALKBH3):​c.389C>G​(p.Pro130Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ALKBH3 NM_139178.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.59

Genes affected

ALKBH3 (HGNC:30141): (alkB homolog 3, alpha-ketoglutarate dependent dioxygenase) The Escherichia coli AlkB protein protects against the cytotoxicity of methylating agents by repair of the specific DNA lesions generated in single-stranded DNA. ALKBH2 (MIM 610602) and ALKBH3 are E. coli AlkB homologs that catalyze the removal of 1-methyladenine and 3-methylcytosine (Duncan et al., 2002 [PubMed 12486230]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.865

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALKBH3	NM_139178.4	c.389C>G	p.Pro130Arg	missense_variant	Exon 7 of 10	ENST00000302708.9	NP_631917.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALKBH3	ENST00000302708.9	c.389C>G	p.Pro130Arg	missense_variant	Exon 7 of 10	1	NM_139178.4	ENSP00000302232.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461020 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726892

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: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T;T
Eigen	Pathogenic	0.93
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.035	D
MetaRNN	Pathogenic	0.86	D;D
MetaSVM	Benign	-0.77	T
MutationAssessor	Pathogenic	3.3	M;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-7.7	D;D
REVEL	Uncertain	0.47
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		1.0	D;.
Vest4		0.94
MutPred		0.74		Gain of solvent accessibility (P = 0.0055);.;
MVP		0.66
MPC		0.37
ClinPred		1.0	D
GERP RS		5.8
Varity_R		0.91
gMVP		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr11-43913609;