dbSNP rs780079368: ALKBH6:p.Arg167Cys (chr19-36009508-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032878.5(ALKBH6):c.499C>T(p.Arg167Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000877 in 1,254,230 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: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000054 ( 0 hom. )

Consequence

ALKBH6
NM_032878.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.67

Publications

1 publications found

Variant links:

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]

ALKBH6 links:

ENSG00000248101 (HGNC:):

ENSG00000248101 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22051597).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ALKBH6	NM_032878.5	MANE Select	c.499C>T	p.Arg167Cys	missense	Exon 7 of 7	NP_116267.4
ALKBH6	NM_001297701.2		c.499C>T	p.Arg167Cys	missense	Exon 8 of 8	NP_001284630.1	Q3KRA9-1
ALKBH6	NM_001386055.1		c.499C>T	p.Arg167Cys	missense	Exon 7 of 7	NP_001372984.1	Q3KRA9-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ALKBH6	ENST00000378875.8	TSL:1 MANE Select	c.499C>T	p.Arg167Cys	missense	Exon 7 of 7	ENSP00000368152.4	Q3KRA9-1
ALKBH6	ENST00000252984.11	TSL:1	c.499C>T	p.Arg167Cys	missense	Exon 8 of 8	ENSP00000252984.6	Q3KRA9-1
ALKBH6	ENST00000490986.5	TSL:1	n.*192C>T		non_coding_transcript_exon	Exon 7 of 7	ENSP00000435496.1	H0YEC4

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000480

GnomAD2 exomes

AF:

0.0000419

AC:

AN:

23844

AF XY:

0.0000747

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000471

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000544

AC:

AN:

1102174

Hom.:

Cov.:

AF XY:

0.00000383

AC XY:

AN XY:

522624

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23786

American (AMR)

AF:

0.000190

AC:

AN:

10514

Ashkenazi Jewish (ASJ)

AF:

0.0000685

AC:

AN:

14604

East Asian (EAS)

AF:

0.00

AC:

AN:

27720

South Asian (SAS)

AF:

0.0000459

AC:

AN:

21764

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22126

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3902

European-Non Finnish (NFE)

AF:

0.00000214

AC:

AN:

933144

Other (OTH)

AF:

0.00

AC:

AN:

44614

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152056

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41406

American (AMR)

AF:

0.000196

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67992

Other (OTH)

AF:

0.000480

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.00000973

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.57

LIST_S2

Uncertain

0.92

MetaRNN

Benign

0.22

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

PhyloP100

1.7

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-6.1

REVEL

Benign

0.18

Sift

Benign

0.054

Sift4G

Uncertain

0.060

Polyphen

0.035

Vest4

0.25

MutPred

0.68

Gain of catalytic residue at P166 (P = 0.0072)

MVP

0.13

MPC

2.1

ClinPred

0.47

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.32

gMVP

0.82

Mutation Taster

=73/27

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over