chr19-49459734-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_153329.4(ALDH16A1):c.385C>T(p.Arg129Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 1,613,428 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 (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000032 ( 0 hom. )
Consequence
ALDH16A1
NM_153329.4 missense
NM_153329.4 missense
Scores
6
8
5
Clinical Significance
Conservation
PhyloP100: -0.211
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 Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.955
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALDH16A1 | NM_153329.4 | c.385C>T | p.Arg129Trp | missense_variant | 4/17 | ENST00000293350.9 | |
ALDH16A1 | NM_001145396.2 | c.385C>T | p.Arg129Trp | missense_variant | 4/16 | ||
ALDH16A1 | XM_011526441.1 | c.298C>T | p.Arg100Trp | missense_variant | 4/17 | ||
ALDH16A1 | XM_047438163.1 | c.298C>T | p.Arg100Trp | missense_variant | 5/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALDH16A1 | ENST00000293350.9 | c.385C>T | p.Arg129Trp | missense_variant | 4/17 | 1 | NM_153329.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152194Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000280 AC: 7AN: 250194Hom.: 1 AF XY: 0.00000738 AC XY: 1AN XY: 135540
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GnomAD4 exome AF: 0.0000322 AC: 47AN: 1461234Hom.: 0 Cov.: 32 AF XY: 0.0000289 AC XY: 21AN XY: 726920
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152194Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74348
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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 27, 2021 | The c.385C>T (p.R129W) alteration is located in exon 4 (coding exon 4) of the ALDH16A1 gene. This alteration results from a C to T substitution at nucleotide position 385, causing the arginine (R) at amino acid position 129 to be replaced by a tryptophan (W). 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
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Benign
Dann
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D;D;N
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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