chr2-134846227-T-C

Variant names:

• chr2-134846227-T-C
• rs1942052
• NM_138326.3:c.102+950T>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.102+950T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,078 control chromosomes in the GnomAD database, including 4,004 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 0.22 (4004 hom., cov: 32)
• Consequence: ACMSD NM_138326.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105
• Publications: 8 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=-0.71).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACMSD	NM_138326.3	c.102+950T>C		intron_variant	Intron 2 of 9	ENST00000356140.10	NP_612199.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACMSD	ENST00000356140.10	c.102+950T>C		intron_variant	Intron 2 of 9	1	NM_138326.3	ENSP00000348459.5

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32703 AN: 151960 Hom.: 4005 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.0993

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.215 AC: 32719 AN: 152078 Hom.: 4004 Cov.: 32 AF XY: 0.220 AC XY: 16375 AN XY: 74326

African (AFR) AF: 0.159 AC: 6605 AN: 41500

American (AMR) AF: 0.275 AC: 4206 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 1506 AN: 3470

East Asian (EAS) AF: 0.0997 AC: 516 AN: 5176

South Asian (SAS) AF: 0.223 AC: 1074 AN: 4826

European-Finnish (FIN) AF: 0.254 AC: 2684 AN: 10560

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15148 AN: 67958

Other (OTH) AF: 0.268 AC: 564 AN: 2106

Alfa AF: 0.231 Hom.: 2309

Bravo AF: 0.211

Asia WGS AF: 0.155 AC: 536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	5.9
DANN	Benign	0.89
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1942052; hg19: chr2-135603797; COSMIC: COSV51610006;