chr19-49459753-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_153329.4(ALDH16A1):c.404G>A(p.Arg135Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000118 in 1,613,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00047 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000081 ( 0 hom. )
Consequence
ALDH16A1
NM_153329.4 missense
NM_153329.4 missense
Scores
1
12
6
Clinical Significance
Conservation
PhyloP100: 5.09
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]
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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=0.13409004).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALDH16A1 | NM_153329.4 | c.404G>A | p.Arg135Gln | missense_variant | 4/17 | ENST00000293350.9 | |
ALDH16A1 | NM_001145396.2 | c.404G>A | p.Arg135Gln | missense_variant | 4/16 | ||
ALDH16A1 | XM_011526441.1 | c.317G>A | p.Arg106Gln | missense_variant | 4/17 | ||
ALDH16A1 | XM_047438163.1 | c.317G>A | p.Arg106Gln | missense_variant | 5/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALDH16A1 | ENST00000293350.9 | c.404G>A | p.Arg135Gln | missense_variant | 4/17 | 1 | NM_153329.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000467 AC: 71AN: 152160Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.000204 AC: 51AN: 250414Hom.: 0 AF XY: 0.000214 AC XY: 29AN XY: 135610
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GnomAD4 exome AF: 0.0000814 AC: 119AN: 1461402Hom.: 0 Cov.: 32 AF XY: 0.0000839 AC XY: 61AN XY: 726984
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GnomAD4 genome ? AF: 0.000466 AC: 71AN: 152278Hom.: 0 Cov.: 32 AF XY: 0.000416 AC XY: 31AN XY: 74452
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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 | Sep 16, 2021 | The c.404G>A (p.R135Q) 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 404, causing the arginine (R) at amino acid position 135 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;T
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at