chr11-67663274-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001393402.2(ALDH3B2):​c.1099G>A​(p.Asp367Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,613,742 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ALDH3B2
NM_001393402.2 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.977
Variant links:
Genes affected
ALDH3B2 (HGNC:411): (aldehyde dehydrogenase 3 family member B2) This gene encodes a member of the aldehyde dehydrogenase family, a group of isozymes that may play a major role in the detoxification of aldehydes generated by alcohol metabolism and lipid peroxidation. The gene of this particular family member is over 10 kb in length. Altered methylation patterns at this locus have been observed in spermatozoa derived from patients exhibiting reduced fecundity. [provided by RefSeq, Aug 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.082378894).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ALDH3B2NM_001393402.2 linkc.1099G>A p.Asp367Asn missense_variant Exon 10 of 10 ENST00000673966.2 NP_001380331.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ALDH3B2ENST00000673966.2 linkc.1099G>A p.Asp367Asn missense_variant Exon 10 of 10 NM_001393402.2 ENSP00000501254.1 P48448
ALDH3B2ENST00000530069.6 linkc.1099G>A p.Asp367Asn missense_variant Exon 10 of 10 1 ENSP00000431595.1 P48448
ALDH3B2ENST00000349015.7 linkc.1099G>A p.Asp367Asn missense_variant Exon 10 of 10 5 ENSP00000255084.3 P48448
ALDH3B2ENST00000531248.1 linkc.284G>A p.Arg95Gln missense_variant Exon 3 of 3 5 ENSP00000435476.1 H0YEC0

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152178
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
250706
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135430
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000869
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS 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:
0.0000185
AC:
27
AN:
1461564
Hom.:
0
Cov.:
32
AF XY:
0.0000165
AC XY:
12
AN XY:
727068
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000378
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152178
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 08, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1099G>A (p.D367N) alteration is located in exon 10 (coding exon 8) of the ALDH3B2 gene. This alteration results from a G to A substitution at nucleotide position 1099, causing the aspartic acid (D) at amino acid position 367 to be replaced by an asparagine (N). 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
0.085
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
0.90
DANN
Benign
0.87
DEOGEN2
Benign
0.013
T;T
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.048
N
LIST_S2
Benign
0.47
.;T
M_CAP
Benign
0.075
D
MetaRNN
Benign
0.082
T;T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
1.0
L;L
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-1.4
N;N
REVEL
Benign
0.15
Sift
Benign
0.17
T;T
Sift4G
Benign
0.22
T;T
Polyphen
0.0070
B;B
Vest4
0.11
MutPred
0.28
Loss of catalytic residue at D367 (P = 0.0308);Loss of catalytic residue at D367 (P = 0.0308);
MVP
0.44
MPC
0.19
ClinPred
0.042
T
GERP RS
-7.5
Varity_R
0.036
gMVP
0.42

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: rs757916431; hg19: chr11-67430745; COSMIC: COSV62427603; COSMIC: COSV62427603; API