19-36009408-T-C

Variant names:

• chr19-36009408-T-C
• rs942396686
• NM_032878.5:c.599A>G

Variant summary

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

The NM_032878.5(ALKBH6):​c.599A>G​(p.Asn200Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,097,092 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. N200T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: ALKBH6 NM_032878.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.13
• 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=0.29523945).

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.599A>G	p.Asn200Ser	missense	Exon 7 of 7	NP_116267.4
	ALKBH6	NM_001297701.2		c.599A>G	p.Asn200Ser	missense	Exon 8 of 8	NP_001284630.1	Q3KRA9-1
	ALKBH6	NM_001386055.1		c.599A>G	p.Asn200Ser	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.599A>G	p.Asn200Ser	missense	Exon 7 of 7	ENSP00000368152.4	Q3KRA9-1
	ALKBH6	ENST00000252984.11	TSL:1	c.599A>G	p.Asn200Ser	missense	Exon 8 of 8	ENSP00000252984.6	Q3KRA9-1
	ALKBH6	ENST00000490986.5	TSL:1	n.*292A>G		non_coding_transcript_exon	Exon 7 of 7	ENSP00000435496.1	H0YEC4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1097092 Hom.: 0 Cov.: 30 AF XY: 0.00000192 AC XY: 1 AN XY: 519900

African (AFR) AF: 0.00 AC: 0 AN: 22996

American (AMR) AF: 0.00 AC: 0 AN: 8444

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14614

East Asian (EAS) AF: 0.0000376 AC: 1 AN: 26562

South Asian (SAS) AF: 0.00 AC: 0 AN: 24424

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3050

European-Non Finnish (NFE) AF: 0.00000107 AC: 1 AN: 930294

Other (OTH) AF: 0.00 AC: 0 AN: 44420

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.73	T
M_CAP	Pathogenic	0.50	D
MetaRNN	Benign	0.30	T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.1
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.38
Sift	Benign	0.070	T
Sift4G	Uncertain	0.056	T
Polyphen		0.0050	B
Vest4		0.17
MutPred		0.32		Gain of glycosylation at N200 (P = 0.0017)
MVP		0.35
MPC		2.5
ClinPred		0.46	T
GERP RS		5.5
Varity_R		0.089
gMVP		0.33
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs942396686; hg19: chr19-36500310;