chr2-134867630-A-G

Variant summary

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

The ENST00000356140.10(ACMSD):ā€‹c.538A>Gā€‹(p.Met180Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000055 ( 0 hom. )

Consequence

ACMSD
ENST00000356140.10 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.72
Variant links:
Genes affected
ACMSD (HGNC:19288): (aminocarboxymuconate semialdehyde decarboxylase) The neuronal excitotoxin quinolinate is an intermediate in the de novo synthesis pathway of NAD from tryptophan, and has been implicated in the pathogenesis of several neurodegenerative disorders. Quinolinate is derived from alpha-amino-beta-carboxy-muconate-epsilon-semialdehyde (ACMS). ACMSD (ACMS decarboxylase; EC 4.1.1.45) can divert ACMS to a benign catabolite and thus prevent the accumulation of quinolinate from ACMS.[supplied by OMIM, Oct 2004]
CCNT2-AS1 (HGNC:40130): (CCNT2 antisense RNA 1)

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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 Protein UniProt
ACMSDNM_138326.3 linkuse as main transcriptc.538A>G p.Met180Val missense_variant 6/10 ENST00000356140.10 NP_612199.2
CCNT2-AS1NR_036549.1 linkuse as main transcriptn.408T>C non_coding_transcript_exon_variant 5/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ACMSDENST00000356140.10 linkuse as main transcriptc.538A>G p.Met180Val missense_variant 6/101 NM_138326.3 ENSP00000348459 P1Q8TDX5-1
CCNT2-AS1ENST00000392929.6 linkuse as main transcriptn.316T>C non_coding_transcript_exon_variant 3/44

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251196
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135768
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000116
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:
0.00000547
AC:
8
AN:
1461570
Hom.:
0
Cov.:
31
AF XY:
0.00000688
AC XY:
5
AN XY:
727108
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000895
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

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 GeneticsMay 30, 2024The c.538A>G (p.M180V) alteration is located in exon 6 (coding exon 6) of the ACMSD gene. This alteration results from a A to G substitution at nucleotide position 538, causing the methionine (M) at amino acid position 180 to be replaced by a valine (V). 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
0.11
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
20
DANN
Benign
0.95
DEOGEN2
Benign
0.031
T;.
Eigen
Benign
-0.14
Eigen_PC
Benign
0.071
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.87
D;D
M_CAP
Benign
0.0029
T
MetaRNN
Benign
0.22
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L;.
MutationTaster
Benign
0.98
N;N;N
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-1.0
N;N
REVEL
Benign
0.073
Sift
Benign
0.29
T;T
Sift4G
Benign
0.34
T;T
Polyphen
0.0030
B;.
Vest4
0.46
MutPred
0.47
Loss of MoRF binding (P = 0.2106);.;
MVP
0.20
MPC
0.075
ClinPred
0.30
T
GERP RS
5.4
Varity_R
0.23
gMVP
0.66

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.21
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.21
Position offset: 42

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: rs969976018; hg19: chr2-135625200; API