Genetic Variant NM_032878.5:c.583G>A (chr19-36009424-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_032878.5(ALKBH6):c.583G>A(p.Ala195Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000183 in 1,092,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)

Exomes 𝑓: 0.0000018 ( 0 hom. )

Consequence

ALKBH6
NM_032878.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.15

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.035207957).

BP6

Variant 19-36009424-C-T is Benign according to our data. Variant chr19-36009424-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3856625.Status of the report is criteria_provided_single_submitter, 1 stars.

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.583G>A	p.Ala195Thr	missense	Exon 7 of 7	NP_116267.4
ALKBH6	NM_001297701.2		c.583G>A	p.Ala195Thr	missense	Exon 8 of 8	NP_001284630.1	Q3KRA9-1
ALKBH6	NM_001386055.1		c.583G>A	p.Ala195Thr	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.583G>A	p.Ala195Thr	missense	Exon 7 of 7	ENSP00000368152.4	Q3KRA9-1
ALKBH6	ENST00000252984.11	TSL:1	c.583G>A	p.Ala195Thr	missense	Exon 8 of 8	ENSP00000252984.6	Q3KRA9-1
ALKBH6	ENST00000490986.5	TSL:1	n.*276G>A		non_coding_transcript_exon	Exon 7 of 7	ENSP00000435496.1	H0YEC4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000183

AC:

AN:

1092880

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

517282

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23052

American (AMR)

AF:

0.00

AC:

AN:

8492

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14554

East Asian (EAS)

AF:

0.00

AC:

AN:

26622

South Asian (SAS)

AF:

0.0000883

AC:

AN:

22638

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21902

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3100

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

928272

Other (OTH)

AF:

0.00

AC:

AN:

44248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.072

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.021

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.0044

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0089

LIST_S2

Benign

0.56

M_CAP

Benign

0.014

MetaRNN

Benign

0.035

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.36

PhyloP100

-3.1

PrimateAI

Uncertain

0.66

PROVEAN

Benign

1.2

REVEL

Benign

0.080

Sift

Benign

0.63

Sift4G

Benign

0.59

Polyphen

0.0

Vest4

0.047

MutPred

0.34

Gain of glycosylation at A195 (P = 7e-04)

MVP

0.048

MPC

1.5

ClinPred

0.045

GERP RS

-10

Varity_R

0.025

gMVP

0.33

Mutation Taster

=91/9

polymorphism

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over