17-3476162-G-T
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Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1PS1_ModeratePM2PP5_Moderate
The NM_000049.4(ASPA):c.3G>T(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.000000685 in 1,460,832 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 Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
ASPA
NM_000049.4 start_lost
NM_000049.4 start_lost
Scores
9
4
3
Clinical Significance
Conservation
PhyloP100: 6.85
Genes affected
ASPA (HGNC:756): (aspartoacylase) This gene encodes an enzyme that catalyzes the conversion of N-acetyl_L-aspartic acid (NAA) to aspartate and acetate. NAA is abundant in the brain where hydrolysis by aspartoacylase is thought to help maintain white matter. This protein is an NAA scavenger in other tissues. Mutations in this gene cause Canavan disease. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]
SPATA22 (HGNC:30705): (spermatogenesis associated 22) Predicted to be involved in regulation of meiotic cell cycle. Predicted to act upstream of or within several processes, including fertilization; gamete generation; and meiosis I cell cycle process. Predicted to be located in chromosome. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 14 ACMG points.
PVS1
Start lost variant, no new inframe start found.
PS1
Another start lost variant in NM_000049.4 (ASPA) was described as [Pathogenic] in Lovd
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 17-3476162-G-T is Pathogenic according to our data. Variant chr17-3476162-G-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 813437.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ASPA | NM_000049.4 | c.3G>T | p.Met1? | start_lost | 1/6 | ENST00000263080.3 | NP_000040.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ASPA | ENST00000263080.3 | c.3G>T | p.Met1? | start_lost | 1/6 | 1 | NM_000049.4 | ENSP00000263080 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460832Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726802
GnomAD4 exome
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1
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30
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1
AN XY:
726802
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Spongy degeneration of central nervous system Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D;D
PROVEAN
Benign
.;N;N
REVEL
Pathogenic
Sift
Pathogenic
.;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
0.92
.;P;P
Vest4
0.94, 0.94
MutPred
Loss of disorder (P = 0.1492);Loss of disorder (P = 0.1492);Loss of disorder (P = 0.1492);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at