17-50426347-G-A

Variant names:

• chr17-50426347-G-A
• rs1221218095
• NM_025149.6:c.86G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025149.6(ACSF2):​c.86G>A​(p.Arg29Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000394 in 1,269,276 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000039 (0 hom.)
• Consequence: ACSF2 NM_025149.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.50

Genes affected

ACSF2 (HGNC:26101): (acyl-CoA synthetase family member 2) Enables medium-chain fatty acid-CoA ligase activity. Predicted to be involved in fatty acid metabolic process. Predicted to be located in mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19248763).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSF2	NM_025149.6	c.86G>A	p.Arg29Gln	missense_variant	Exon 1 of 16	ENST00000300441.9	NP_079425.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSF2	ENST00000300441.9	c.86G>A	p.Arg29Gln	missense_variant	Exon 1 of 16	1	NM_025149.6	ENSP00000300441.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000394 AC: 5 AN: 1269276 Hom.: 0 Cov.: 31 AF XY: 0.00000642 AC XY: 4 AN XY: 623450

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: 0.00000494

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.86G>A (p.R29Q) alteration is located in exon 1 (coding exon 1) of the ACSF2 gene. This alteration results from a G to A substitution at nucleotide position 86, causing the arginine (R) at amino acid position 29 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	17
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.086	T;.;T;.;.
Eigen	Benign	-0.021
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.15	N
LIST_S2	Uncertain	0.88	D;D;D;T;D
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.19	T;T;T;T;T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	0.63	N;.;.;N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.39	N;N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.12	T;T;D;D;D
Sift4G	Benign	0.27	T;T;T;T;T
Polyphen		0.037	B;.;D;.;.
Vest4		0.29
MutPred		0.38		Loss of MoRF binding (P = 0.0464);Loss of MoRF binding (P = 0.0464);Loss of MoRF binding (P = 0.0464);Loss of MoRF binding (P = 0.0464);Loss of MoRF binding (P = 0.0464);
MVP		0.62
MPC		0.42
ClinPred		0.36	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.063
gMVP		0.32

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: rs1221218095; hg19: chr17-48503708;