3-38129319-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001607.4(ACAA1):​c.516G>C​(p.Glu172Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,613,526 control chromosomes in the GnomAD database, including 18,930 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1645 hom., cov: 32)
  • Exomes 𝑓: 0.15 (17285 hom.)
• Consequence: ACAA1 NM_001607.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0011505485).
• BP6: Variant 3-38129319-C-G is Benign according to our data. Variant chr3-38129319-C-G is described in ClinVar as Benign. ClinVar VariationId is 1277354.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

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>C	p.Glu172Asp	missense	Exon 6 of 12	NP_001598.1	P09110-1
	ACAA1	NM_001130410.2		c.447-1453G>C		intron	N/A	NP_001123882.1	P09110-2
	ACAA1	NR_024024.2		n.565G>C		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>C	p.Glu172Asp	missense	Exon 6 of 12	ENSP00000333664.8	P09110-1
	ACAA1	ENST00000301810.11	TSL:1	c.447-1453G>C		intron	N/A	ENSP00000301810.7	P09110-2
	ACAA1	ENST00000411549.5	TSL:1	n.*11G>C		non_coding_transcript_exon	Exon 5 of 10	ENSP00000414021.1	B4DVF4

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19632 AN: 152104 Hom.: 1647 Cov.: 32

Gnomad AFR AF: 0.0421

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.0920

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.121

GnomAD2 exomes AF: 0.157 AC: 39481 AN: 251324 AF XY: 0.151

Gnomad AFR exome AF: 0.0429

Gnomad AMR exome AF: 0.199

Gnomad ASJ exome AF: 0.149

Gnomad EAS exome AF: 0.360

Gnomad FIN exome AF: 0.185

Gnomad NFE exome AF: 0.145

Gnomad OTH exome AF: 0.135

GnomAD4 exome AF: 0.146 AC: 212807 AN: 1461304 Hom.: 17285 Cov.: 32 AF XY: 0.144 AC XY: 104463 AN XY: 726982

African (AFR) AF: 0.0378 AC: 1264 AN: 33476

American (AMR) AF: 0.193 AC: 8643 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 3928 AN: 26128

East Asian (EAS) AF: 0.330 AC: 13109 AN: 39698

South Asian (SAS) AF: 0.0812 AC: 7006 AN: 86254

European-Finnish (FIN) AF: 0.182 AC: 9711 AN: 53394

Middle Eastern (MID) AF: 0.0491 AC: 283 AN: 5768

European-Non Finnish (NFE) AF: 0.145 AC: 160642 AN: 1111500

Other (OTH) AF: 0.136 AC: 8221 AN: 60380

GnomAD4 genome AF: 0.129 AC: 19630 AN: 152222 Hom.: 1645 Cov.: 32 AF XY: 0.131 AC XY: 9772 AN XY: 74418

African (AFR) AF: 0.0420 AC: 1743 AN: 41540

American (AMR) AF: 0.182 AC: 2776 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 506 AN: 3472

East Asian (EAS) AF: 0.348 AC: 1800 AN: 5174

South Asian (SAS) AF: 0.0925 AC: 446 AN: 4822

European-Finnish (FIN) AF: 0.190 AC: 2016 AN: 10598

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10049 AN: 68004

Other (OTH) AF: 0.119 AC: 252 AN: 2112

Alfa AF: 0.136 Hom.: 1198

Bravo AF: 0.124

TwinsUK AF: 0.145 AC: 537

ALSPAC AF: 0.155 AC: 596

ESP6500AA AF: 0.0468 AC: 206

ESP6500EA AF: 0.145 AC: 1251

ExAC AF: 0.153 AC: 18563

Asia WGS AF: 0.171 AC: 594 AN: 3478

EpiCase AF: 0.133

EpiControl AF: 0.136

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	ACAA1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.0012	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.26	N
PhyloP100		0.28
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.21
Sift	Benign	0.25	T
Sift4G	Benign	0.34	T
Polyphen		0.0	B
Vest4		0.060
MutPred		0.15		Loss of sheet (P = 0.0817)
MPC		0.31
ClinPred		0.0035	T
GERP RS		1.7
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		3.7
Varity_R		0.13
gMVP		0.42
Mutation Taster		=94/6	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: rs156265; hg19: chr3-38170810; COSMIC: COSV57171168; COSMIC: COSV57171168;