11-43882689-G-C

Variant names:

• chr11-43882689-G-C
• rs1457379817
• NM_139178.4:c.37G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_139178.4(ALKBH3):​c.37G>C​(p.Ala13Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A13S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ALKBH3 NM_139178.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.72
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29249597).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139178.4. 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
	ALKBH3	NM_139178.4	MANE Select	c.37G>C	p.Ala13Pro	missense	Exon 2 of 10	NP_631917.1	Q96Q83-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALKBH3	ENST00000302708.9	TSL:1 MANE Select	c.37G>C	p.Ala13Pro	missense	Exon 2 of 10	ENSP00000302232.4	Q96Q83-1
	ALKBH3	ENST00000532962.5	TSL:1	n.37G>C		non_coding_transcript_exon	Exon 2 of 10	ENSP00000434832.1	E9PN35
	ALKBH3	ENST00000856730.1		c.37G>C	p.Ala13Pro	missense	Exon 2 of 10	ENSP00000526789.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000282 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.063
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		4.7
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.13
Sift	Benign	0.26	T
Sift4G	Benign	0.24	T
Polyphen		0.0010	B
Vest4		0.54
MutPred		0.23		Gain of relative solvent accessibility (P = 0.0215)
MVP		0.59
MPC		0.22
ClinPred		0.96	D
GERP RS		5.4
PromoterAI		-0.030	Neutral
Varity_R		0.25
gMVP		0.39
Mutation Taster		=77/23	polymorphism

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: rs1457379817; hg19: chr11-43904239;