2-134840058-T-G

Position:

• chr2-134840058-T-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACMSD	NM_138326.3	c.57+1319T>G		intron_variant		ENST00000356140.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACMSD	ENST00000356140.10	c.57+1319T>G		intron_variant		1	NM_138326.3	P1
CCNT2-AS1	ENST00000392929.6	n.426+27462A>C		intron_variant, non_coding_transcript_variant		4

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

Gnomad4 AFR AF: 0.565

Gnomad4 AMR AF: 0.629

Gnomad4 ASJ AF: 0.750

Gnomad4 EAS AF: 0.610

Gnomad4 SAS AF: 0.692

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.599

Alfa AF: 0.486 Hom.: 22479

Bravo AF: 0.526

Asia WGS AF: 0.657 AC: 2283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs10496731; hg19: chr2-135597628;