chr19-36010991-T-G

Variant names:

• chr19-36010991-T-G
• rs1555786344
• NM_032878.5:c.239A>C

Variant summary

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

The NM_032878.5(ALKBH6):​c.239A>C​(p.Gln80Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,404 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000014 (0 hom.)
• Consequence: ALKBH6 NM_032878.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.06
• 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=0.38262418).

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.239A>C	p.Gln80Pro	missense	Exon 5 of 7	NP_116267.4
	ALKBH6	NM_001297701.2		c.239A>C	p.Gln80Pro	missense	Exon 6 of 8	NP_001284630.1	Q3KRA9-1
	ALKBH6	NM_001386055.1		c.239A>C	p.Gln80Pro	missense	Exon 5 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.239A>C	p.Gln80Pro	missense	Exon 5 of 7	ENSP00000368152.4	Q3KRA9-1
	ALKBH6	ENST00000252984.11	TSL:1	c.239A>C	p.Gln80Pro	missense	Exon 6 of 8	ENSP00000252984.6	Q3KRA9-1
	ALKBH6	ENST00000392183.7	TSL:1	n.303A>C		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461404 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726996

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53322

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111848

Other (OTH) AF: 0.00 AC: 0 AN: 60334

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	Pathogenic	0.62
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Benign	0.021
Eigen_PC	Benign	0.062
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.1
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.19
Sift	Benign	0.034	D
Sift4G	Benign	0.080	T
Polyphen		0.071	B
Vest4		0.55
MutPred		0.52		Loss of MoRF binding (P = 0.0795)
MVP		0.36
MPC		0.38
ClinPred		0.81	D
GERP RS		3.1
Varity_R		0.89
gMVP		0.86
Mutation Taster		=57/43	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: rs1555786344; hg19: chr19-36501893;