NM_139178.4:c.144T>G

Variant names:

• chr11-43883149-T-G
• rs1951723390
• NM_139178.4:c.144T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_139178.4(ALKBH3):​c.144T>G​(p.His48Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ALKBH3 NM_139178.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.470
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.036260515).

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.144T>G	p.His48Gln	missense	Exon 3 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.144T>G	p.His48Gln	missense	Exon 3 of 10	ENSP00000302232.4	Q96Q83-1
	ALKBH3	ENST00000532962.5	TSL:1	n.144T>G		non_coding_transcript_exon	Exon 3 of 10	ENSP00000434832.1	E9PN35
	ALKBH3	ENST00000856730.1		c.144T>G	p.His48Gln	missense	Exon 3 of 10	ENSP00000526789.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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	Benign	0.080
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	7.0
DANN	Benign	0.76
DEOGEN2	Benign	0.046	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.47
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.011
Sift	Benign	0.38	T
Sift4G	Benign	0.69	T
Polyphen		0.0	B
Vest4		0.20
MutPred		0.20		Gain of MoRF binding (P = 0.0731)
MVP		0.24
MPC		0.057
ClinPred		0.035	T
GERP RS		-1.3
Varity_R		0.031
gMVP		0.20
Mutation Taster		=96/4	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: rs1951723390; hg19: chr11-43904699;