NM_138775.3:c.1675C>A

Variant names:

• chr11-107504978-G-T
• NM_138775.3:c.1675C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_138775.3(ALKBH8):​c.1675C>A​(p.Arg559Ser) 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. 15/21 in silico tools predict 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)
• Consequence: ALKBH8 NM_138775.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.246

Genes affected

ALKBH8 (HGNC:25189): (alkB homolog 8, tRNA methyltransferase) Enables tRNA (uracil) methyltransferase activity; tRNA binding activity; and zinc ion binding activity. Involved in cellular response to DNA damage stimulus; tRNA methylation; and tRNA wobble uridine modification. Located in cytosol and nuclear body. Implicated in autosomal recessive non-syndromic intellectual disability. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05045271).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALKBH8	NM_138775.3	c.1675C>A	p.Arg559Ser	missense_variant	Exon 12 of 12	ENST00000428149.7	NP_620130.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALKBH8	ENST00000428149.7	c.1675C>A	p.Arg559Ser	missense_variant	Exon 12 of 12	1	NM_138775.3	ENSP00000415885.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000165 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.014
DANN	Benign	0.22
DEOGEN2	Benign	0.022	T;T;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.10	.;T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.050	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-2.6	N;N;.
PrimateAI	Benign	0.19	T
PROVEAN	Benign	0.48	N;N;N
REVEL	Benign	0.035
Sift	Benign	0.77	T;T;T
Sift4G	Benign	0.74	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.060
MutPred		0.32		Gain of phosphorylation at R559 (P = 0.0194);Gain of phosphorylation at R559 (P = 0.0194);.;
MVP		0.030
MPC		0.0098
ClinPred		0.034	T
GERP RS		-2.0
Varity_R		0.062
gMVP		0.23

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: chr11-107375704;