NM_001607.4:c.128G>A

Variant names:

• chr3-38136908-C-T
• NM_001607.4:c.128G>A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001607.4(ACAA1):​c.128G>A​(p.Gly43Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,383,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: ACAA1 NM_001607.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15

Genes affected

ACAA1 (HGNC:82): (acetyl-CoA acyltransferase 1) This gene encodes an enzyme operative in the beta-oxidation system of the peroxisomes. Deficiency of this enzyme leads to pseudo-Zellweger syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.951

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACAA1	NM_001607.4	c.128G>A	p.Gly43Glu	missense_variant	Exon 1 of 12	ENST00000333167.13	NP_001598.1
ACAA1	NM_001130410.2	c.128G>A	p.Gly43Glu	missense_variant	Exon 1 of 10		NP_001123882.1
ACAA1	XM_006713122.1	c.128G>A	p.Gly43Glu	missense_variant	Exon 1 of 11		XP_006713185.1
ACAA1	NR_024024.2	n.220G>A		non_coding_transcript_exon_variant	Exon 1 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACAA1	ENST00000333167.13	c.128G>A	p.Gly43Glu	missense_variant	Exon 1 of 12	1	NM_001607.4	ENSP00000333664.8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1383320 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 682570

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.29e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.37
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.71	D;.;D;D;D
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.99	D;D;D;D;D
M_CAP	Pathogenic	0.85	D
MetaRNN	Pathogenic	0.95	D;D;D;D;D
MetaSVM	Pathogenic	0.98	D
MutationAssessor	Uncertain	2.4	M;M;.;.;.
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-1.8	N;N;.;.;N
REVEL	Pathogenic	0.83
Sift	Uncertain	0.0010	D;D;.;.;D
Sift4G	Pathogenic	0.0010	D;D;D;D;D
Polyphen		0.99	D;.;.;.;P
Vest4		0.86
MutPred		0.79		Loss of MoRF binding (P = 0.0312);Loss of MoRF binding (P = 0.0312);Loss of MoRF binding (P = 0.0312);Loss of MoRF binding (P = 0.0312);Loss of MoRF binding (P = 0.0312);
MVP		0.94
MPC		1.3
ClinPred		0.98	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.98
gMVP		0.97

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-38178399;