3-38129319-C-T

Variant names:

• chr3-38129319-C-T
• rs156265
• NM_001607.4:c.516G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001607.4(ACAA1):​c.516G>A​(p.Glu172Glu) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACAA1 NM_001607.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.285
• Publications: 31 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.009).
• BP7: Synonymous conserved (PhyloP=0.285 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001607.4. 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
	ACAA1	NM_001607.4	MANE Select	c.516G>A	p.Glu172Glu	synonymous	Exon 6 of 12	NP_001598.1	P09110-1
	ACAA1	NM_001130410.2		c.447-1453G>A		intron	N/A	NP_001123882.1	P09110-2
	ACAA1	NR_024024.2		n.565G>A		non_coding_transcript_exon	Exon 5 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACAA1	ENST00000333167.13	TSL:1 MANE Select	c.516G>A	p.Glu172Glu	synonymous	Exon 6 of 12	ENSP00000333664.8	P09110-1
	ACAA1	ENST00000301810.11	TSL:1	c.447-1453G>A		intron	N/A	ENSP00000301810.7	P09110-2
	ACAA1	ENST00000411549.5	TSL:1	n.*11G>A		non_coding_transcript_exon	Exon 5 of 10	ENSP00000414021.1	B4DVF4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251324 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1198

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	9.7
DANN	Benign	0.69
PhyloP100		0.28

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: rs156265; hg19: chr3-38170810;