19-36009489-C-T

Variant names:

• chr19-36009489-C-T
• NM_032878.5:c.518G>A

Variant summary

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

The NM_032878.5(ALKBH6):​c.518G>A​(p.Arg173His) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ALKBH6 NM_032878.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.78
• Publications: 0 publications found

Genes affected

ALKBH6 (HGNC:28243): (alkB homolog 6) Predicted to enable dioxygenase activity and metal ion binding activity. Located in focal adhesion and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000248101 (HGNC:):

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=0.346137).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032878.5. 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
	ALKBH6	NM_032878.5	MANE Select	c.518G>A	p.Arg173His	missense	Exon 7 of 7	NP_116267.4
	ALKBH6	NM_001297701.2		c.518G>A	p.Arg173His	missense	Exon 8 of 8	NP_001284630.1	Q3KRA9-1
	ALKBH6	NM_001386055.1		c.518G>A	p.Arg173His	missense	Exon 7 of 7	NP_001372984.1	Q3KRA9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALKBH6	ENST00000378875.8	TSL:1 MANE Select	c.518G>A	p.Arg173His	missense	Exon 7 of 7	ENSP00000368152.4	Q3KRA9-1
	ALKBH6	ENST00000252984.11	TSL:1	c.518G>A	p.Arg173His	missense	Exon 8 of 8	ENSP00000252984.6	Q3KRA9-1
	ALKBH6	ENST00000490986.5	TSL:1	n.*211G>A		non_coding_transcript_exon	Exon 7 of 7	ENSP00000435496.1	H0YEC4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1096026 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 519242

African (AFR) AF: 0.00 AC: 0 AN: 23438

American (AMR) AF: 0.00 AC: 0 AN: 9630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14492

East Asian (EAS) AF: 0.00 AC: 0 AN: 27164

South Asian (SAS) AF: 0.00 AC: 0 AN: 21572

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21834

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 929788

Other (OTH) AF: 0.00 AC: 0 AN: 44342

GnomAD4 genome Cov.: 32

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	0.23
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.036	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Benign	0.40	N
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.8
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.11
Sift	Benign	0.035	D
Sift4G	Uncertain	0.054	T
Polyphen		1.0	D
Vest4		0.28
MutPred		0.44		Loss of methylation at R173 (P = 0.0085)
MVP		0.25
MPC		3.1
ClinPred		0.92	D
GERP RS		3.1
Varity_R		0.20
gMVP		0.48
Mutation Taster		=88/12	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

hg19: chr19-36500391;