Variant 19-49459764-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_153329.4(ALDH16A1):c.415G>A(p.Val139Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0005 in 1,613,524 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00049 ( 2 hom. )

Consequence

ALDH16A1
NM_153329.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0100

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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009287775).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ALDH16A1	NM_153329.4 linkuse as main transcript	c.415G>A	p.Val139Ile	missense_variant	4/17	ENST00000293350.9
ALDH16A1	NM_001145396.2 linkuse as main transcript	c.415G>A	p.Val139Ile	missense_variant	4/16
ALDH16A1	XM_011526441.1 linkuse as main transcript	c.328G>A	p.Val110Ile	missense_variant	4/17
ALDH16A1	XM_047438163.1 linkuse as main transcript	c.328G>A	p.Val110Ile	missense_variant	5/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALDH16A1	ENST00000293350.9 linkuse as main transcript	c.415G>A	p.Val139Ile	missense_variant	4/17	1	NM_153329.4	P1	Q8IZ83-1

Frequencies

GnomAD3 genomes

AF:

0.000578

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00169

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000882

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000564

AC:

141

AN:

250138

Hom.:

AF XY:

0.000502

AC XY:

AN XY:

135498

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.000797

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000491

Gnomad FIN exome

AF:

0.00190

Gnomad NFE exome

AF:

0.000655

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000492

AC:

719

AN:

1461212

Hom.:

Cov.:

AF XY:

0.000523

AC XY:

380

AN XY:

726894

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.000689

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000522

Gnomad4 FIN exome

AF:

0.00151

Gnomad4 NFE exome

AF:

0.000500

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.000578

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00169

Gnomad4 NFE

AF:

0.000882

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000590

Hom.:

Bravo

AF:

0.000253

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000593

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000415

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 10, 2023

The c.415G>A (p.V139I) alteration is located in exon 4 (coding exon 4) of the ALDH16A1 gene. This alteration results from a G to A substitution at nucleotide position 415, causing the valine (V) at amino acid position 139 to be replaced by an isoleucine (I). 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

Benign

0.074

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.45

Cadd

Benign

8.0

Dann

Benign

0.45

DEOGEN2

Benign

0.036

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.0093

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.40

N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

0.41

N;N

REVEL

Benign

0.15

Sift

Benign

0.87

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.075

B;.

Vest4

0.12

MVP

0.36

MPC

0.064

ClinPred

0.0063

GERP RS

-0.81

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Varity_R

0.021

gMVP

0.14

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over