chr9-72927171-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000689.5(ALDH1A1):​c.449A>T​(p.Asn150Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,449,120 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ALDH1A1
NM_000689.5 missense

Scores

14
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.46
Variant links:
Genes affected
ALDH1A1 (HGNC:402): (aldehyde dehydrogenase 1 family member A1) The protein encoded by this gene belongs to the aldehyde dehydrogenase family. Aldehyde dehydrogenase is the next enzyme after alcohol dehydrogenase in the major pathway of alcohol metabolism. There are two major aldehyde dehydrogenase isozymes in the liver, cytosolic and mitochondrial, which are encoded by distinct genes, and can be distinguished by their electrophoretic mobility, kinetic properties, and subcellular localization. This gene encodes the cytosolic isozyme. Studies in mice show that through its role in retinol metabolism, this gene may also be involved in the regulation of the metabolic responses to high-fat diet. [provided by RefSeq, Mar 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ALDH1A1NM_000689.5 linkuse as main transcriptc.449A>T p.Asn150Ile missense_variant 5/13 ENST00000297785.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ALDH1A1ENST00000297785.8 linkuse as main transcriptc.449A>T p.Asn150Ile missense_variant 5/131 NM_000689.5 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000412
AC:
1
AN:
242458
Hom.:
0
AF XY:
0.00000760
AC XY:
1
AN XY:
131544
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000342
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000207
AC:
3
AN:
1449120
Hom.:
0
Cov.:
27
AF XY:
0.00000416
AC XY:
3
AN XY:
721448
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000118
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000181
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsOct 02, 2023The c.449A>T (p.N150I) alteration is located in exon 5 (coding exon 5) of the ALDH1A1 gene. This alteration results from a A to T substitution at nucleotide position 449, causing the asparagine (N) at amino acid position 150 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
0.24
BayesDel_addAF
Benign
-0.045
T
BayesDel_noAF
Benign
-0.20
CADD
Uncertain
23
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.79
D;T;T;T
Eigen
Uncertain
0.34
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.95
D;D;D;D
M_CAP
Uncertain
0.087
D
MetaRNN
Uncertain
0.56
D;D;D;D
MetaSVM
Uncertain
-0.090
T
MutationAssessor
Uncertain
2.6
M;.;.;.
MutationTaster
Benign
0.74
N;N
PrimateAI
Benign
0.32
T
PROVEAN
Uncertain
-3.9
D;D;D;D
REVEL
Uncertain
0.36
Sift
Uncertain
0.010
D;D;D;D
Sift4G
Uncertain
0.059
T;T;.;T
Polyphen
0.44
B;.;.;.
Vest4
0.26
MutPred
0.52
Loss of solvent accessibility (P = 0.0193);Loss of solvent accessibility (P = 0.0193);Loss of solvent accessibility (P = 0.0193);Loss of solvent accessibility (P = 0.0193);
MVP
0.59
MPC
1.1
ClinPred
0.92
D
GERP RS
5.9
Varity_R
0.70
gMVP
0.78

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.

Other links and lift over

dbSNP: rs775903305; hg19: chr9-75542087; API