chr19-49461912-C-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_153329.4(ALDH16A1):c.788C>A(p.Ala263Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 1,580,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A263T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

ALDH16A1
NM_153329.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.48

Publications

1 publications found

Variant links:

Genes affected

ALDH16A1 (HGNC:28114): (aldehyde dehydrogenase 16 family member A1) This gene encodes a member of the aldehyde dehydrogenase superfamily. The family members act on aldehyde substrates and use nicotinamide adenine dinucleotide phosphate (NADP) as a cofactor. This gene is conserved in chimpanzee, dog, cow, mouse, rat, and zebrafish. The protein encoded by this gene interacts with maspardin, a protein that when truncated is responsible for Mast syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2010]

ALDH16A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.782

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH16A1	NM_153329.4 link	c.788C>A	p.Ala263Glu	missense_variant	Exon 7 of 17	ENST00000293350.9	NP_699160.2	Q8IZ83-1
ALDH16A1	XM_011526441.1 link	c.701C>A	p.Ala234Glu	missense_variant	Exon 7 of 17		XP_011524743.1
ALDH16A1	XM_047438163.1 link	c.701C>A	p.Ala234Glu	missense_variant	Exon 8 of 18		XP_047294119.1
ALDH16A1	NM_001145396.2 link	c.759+112C>A		intron_variant	Intron 6 of 15		NP_001138868.1	Q8IZ83-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH16A1	ENST00000293350.9 link	c.788C>A	p.Ala263Glu	missense_variant	Exon 7 of 17	1	NM_153329.4	ENSP00000293350.3		Q8IZ83-1

Frequencies

GnomAD3 genomes

AF:

0.0000790

AC:

AN:

151808

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000108

AC:

AN:

193984

AF XY:

0.000104

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000697

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000631

Gnomad NFE exome

AF:

0.000216

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000130

AC:

186

AN:

1428684

Hom.:

Cov.:

AF XY:

0.000114

AC XY:

AN XY:

708258

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32632

American (AMR)

AF:

0.0000501

AC:

AN:

39904

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25400

East Asian (EAS)

AF:

0.00

AC:

AN:

37810

South Asian (SAS)

AF:

0.00

AC:

AN:

82664

European-Finnish (FIN)

AF:

0.0000203

AC:

AN:

49370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5690

European-Non Finnish (NFE)

AF:

0.000160

AC:

175

AN:

1096234

Other (OTH)

AF:

0.000136

AC:

AN:

58980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

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:

0.0000790

AC:

AN:

151808

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74152

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41330

American (AMR)

AF:

0.000131

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5130

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

67900

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.546

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:

0.0000677

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.000109

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 09, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.788C>A (p.A263E) alteration is located in exon 7 (coding exon 7) of the ALDH16A1 gene. This alteration results from a C to A substitution at nucleotide position 788, causing the alanine (A) at amino acid position 263 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.71

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.66

D;D

Eigen

Uncertain

0.27

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.74

T;T

M_CAP

Uncertain

0.10

MetaRNN

Pathogenic

0.78

D;D

MetaSVM

Benign

-0.50

MutationAssessor

Pathogenic

3.2

M;.

PhyloP100

1.5

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-4.5

D;D

REVEL

Uncertain

0.38

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

1.0

D;D

Vest4

0.76

MVP

0.57

MPC

0.45

ClinPred

0.64

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.88

gMVP

0.75

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over