ENST00000392928.5:c.-63T>A

Variant names:

• chr2-134845237-T-A
• ENST00000392928.5:c.-63T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000392928.5(ACMSD):​c.-63T>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACMSD ENST00000392928.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.631
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1456002).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000392928.5. 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.62T>A	p.Phe21Tyr	missense	Exon 2 of 10	NP_612199.2	Q8TDX5-1
	ACMSD	NM_001307983.2		c.-63T>A		5_prime_UTR_premature_start_codon_gain	Exon 3 of 10	NP_001294912.1	A0A0S2Z681
	ACMSD	NM_001307983.2		c.-63T>A		5_prime_UTR	Exon 3 of 10	NP_001294912.1	A0A0S2Z681

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACMSD	ENST00000392928.5	TSL:1	c.-63T>A		5_prime_UTR_premature_start_codon_gain	Exon 3 of 10	ENSP00000376659.1	Q8TDX5-2
	ACMSD	ENST00000356140.10	TSL:1 MANE Select	c.62T>A	p.Phe21Tyr	missense	Exon 2 of 10	ENSP00000348459.5	Q8TDX5-1
	ACMSD	ENST00000392928.5	TSL:1	c.-63T>A		5_prime_UTR	Exon 3 of 10	ENSP00000376659.1	Q8TDX5-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	13
DANN	Benign	0.82
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.38	N
PhyloP100		0.63
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	1.3	N
REVEL	Benign	0.053
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.43
MutPred		0.53		Gain of ubiquitination at K19 (P = 0.064)
MVP		0.25
MPC		0.080
ClinPred		0.066	T
GERP RS		1.2
Varity_R		0.23
gMVP		0.72
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

hg19: chr2-135602807;