NM_138326.3:c.58-2927T>C

Variant names:

• chr2-134842306-T-C
• rs10198552
• NM_138326.3:c.58-2927T>C

Variant summary

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

The NM_138326.3(ACMSD):​c.58-2927T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0596 in 152,078 control chromosomes in the GnomAD database, including 403 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 0.060 (403 hom., cov: 31)
• Consequence: ACMSD NM_138326.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACMSD	NM_138326.3	MANE Select	c.58-2927T>C		intron	N/A	NP_612199.2
	ACMSD	NM_001307983.2		c.-174-2059T>C		intron	N/A	NP_001294912.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACMSD	ENST00000356140.10	TSL:1 MANE Select	c.58-2927T>C		intron	N/A	ENSP00000348459.5
	ACMSD	ENST00000392928.5	TSL:1	c.-174-2059T>C		intron	N/A	ENSP00000376659.1
	CCNT2-AS1	ENST00000392929.6	TSL:4	n.426+25214A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0596 AC: 9052 AN: 151960 Hom.: 400 Cov.: 31

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0411

Gnomad ASJ AF: 0.0683

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.0357

Gnomad FIN AF: 0.0485

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0302

Gnomad OTH AF: 0.0623

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

GnomAD4 genome AF: 0.0596 AC: 9067 AN: 152078 Hom.: 403 Cov.: 31 AF XY: 0.0600 AC XY: 4461 AN XY: 74346

African (AFR) AF: 0.128 AC: 5288 AN: 41452

American (AMR) AF: 0.0411 AC: 628 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0683 AC: 237 AN: 3472

East Asian (EAS) AF: 0.00290 AC: 15 AN: 5176

South Asian (SAS) AF: 0.0359 AC: 173 AN: 4816

European-Finnish (FIN) AF: 0.0485 AC: 513 AN: 10584

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0303 AC: 2057 AN: 67980

Other (OTH) AF: 0.0626 AC: 132 AN: 2108

Alfa AF: 0.0387 Hom.: 802

Bravo AF: 0.0628

Asia WGS AF: 0.0390 AC: 136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.6
DANN	Benign	0.68
PhyloP100		-0.037
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs10198552; hg19: chr2-135599876;