19-36010588-C-T

Variant names:

• chr19-36010588-C-T
• NM_032878.5:c.432G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_198867.1(ALKBH6):​c.478G>A​(p.Gly160Arg) 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. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ALKBH6 NM_198867.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.224
• 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: 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=0.12023899).
• BP6: Variant 19-36010588-C-T is Benign according to our data. Variant chr19-36010588-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3286915.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198867.1. 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.432G>A	p.Glu144Glu	synonymous	Exon 6 of 7	NP_116267.4
	ALKBH6	NM_198867.1		c.478G>A	p.Gly160Arg	missense	Exon 6 of 7	NP_942567.1
	ALKBH6	NM_001297701.2		c.432G>A	p.Glu144Glu	synonymous	Exon 7 of 8	NP_001284630.1	Q3KRA9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALKBH6	ENST00000378875.8	TSL:1 MANE Select	c.432G>A	p.Glu144Glu	synonymous	Exon 6 of 7	ENSP00000368152.4	Q3KRA9-1
	ALKBH6	ENST00000252984.11	TSL:1	c.432G>A	p.Glu144Glu	synonymous	Exon 7 of 8	ENSP00000252984.6	Q3KRA9-1
	ALKBH6	ENST00000392183.7	TSL:1	n.706G>A		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.18
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	1.7
DANN	Benign	0.82
DEOGEN2	Benign	0.0078	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.27	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.83	T
PhyloP100		0.22
PROVEAN	Benign	0.080	N
REVEL	Benign	0.028
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.32
MutPred		0.38		Gain of solvent accessibility (P = 0.0037)
MVP		0.27
ClinPred		0.13	T
GERP RS		3.2
Mutation Taster		=91/9	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: chr19-36501490;