2-134840058-T-G

Variant names:

• chr2-134840058-T-G
• rs10496731
• NM_138326.3:c.57+1319T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138326.3(ACMSD):​c.57+1319T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 150,746 control chromosomes in the GnomAD database, including 20,646 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (20646 hom., cov: 27)
• Consequence: ACMSD NM_138326.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540
• Publications: 14 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138326.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACMSD	NM_138326.3	MANE Select	c.57+1319T>G		intron	N/A	NP_612199.2	Q8TDX5-1
	ACMSD	NM_001307983.2		c.-175+1319T>G		intron	N/A	NP_001294912.1	A0A0S2Z681

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACMSD	ENST00000356140.10	TSL:1 MANE Select	c.57+1319T>G		intron	N/A	ENSP00000348459.5	Q8TDX5-1
	ACMSD	ENST00000392928.5	TSL:1	c.-175+1319T>G		intron	N/A	ENSP00000376659.1	Q8TDX5-2
	ACMSD	ENST00000904289.1		c.57+1319T>G		intron	N/A	ENSP00000574348.1

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77104 AN: 150630 Hom.: 20614 Cov.: 27

Gnomad AFR AF: 0.565

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.750

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.595

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.512 AC: 77198 AN: 150746 Hom.: 20646 Cov.: 27 AF XY: 0.520 AC XY: 38236 AN XY: 73588

African (AFR) AF: 0.565 AC: 23120 AN: 40928

American (AMR) AF: 0.629 AC: 9504 AN: 15120

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 2590 AN: 3454

East Asian (EAS) AF: 0.610 AC: 3121 AN: 5120

South Asian (SAS) AF: 0.692 AC: 3261 AN: 4710

European-Finnish (FIN) AF: 0.429 AC: 4457 AN: 10382

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29307 AN: 67754

Other (OTH) AF: 0.599 AC: 1242 AN: 2074

Alfa AF: 0.490 Hom.: 38564

Bravo AF: 0.526

Asia WGS AF: 0.657 AC: 2283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.55
PhyloP100		-0.054
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10496731; hg19: chr2-135597628;