17-50426347-G-C

Variant names:

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

Variant summary

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

The NM_025149.6(ACSF2):​c.86G>C​(p.Arg29Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000788 in 1,269,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R29Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: ACSF2 NM_025149.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50
• Publications: 0 publications found

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

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=0.24605459).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025149.6. 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
	ACSF2	NM_025149.6	MANE Select	c.86G>C	p.Arg29Pro	missense	Exon 1 of 16	NP_079425.3
	ACSF2	NM_001288968.2		c.86G>C	p.Arg29Pro	missense	Exon 1 of 17	NP_001275897.1	Q96CM8-2
	ACSF2	NM_001288969.2		c.86G>C	p.Arg29Pro	missense	Exon 1 of 16	NP_001275898.1	Q96CM8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSF2	ENST00000300441.9	TSL:1 MANE Select	c.86G>C	p.Arg29Pro	missense	Exon 1 of 16	ENSP00000300441.4	Q96CM8-1
	ACSF2	ENST00000427954.6	TSL:2	c.86G>C	p.Arg29Pro	missense	Exon 1 of 17	ENSP00000401831.2	Q96CM8-2
	ACSF2	ENST00000942398.1		c.86G>C	p.Arg29Pro	missense	Exon 1 of 17	ENSP00000612457.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.88e-7 AC: 1 AN: 1269278 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 623452

African (AFR) AF: 0.00 AC: 0 AN: 26412

American (AMR) AF: 0.00 AC: 0 AN: 21688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30350

South Asian (SAS) AF: 0.00 AC: 0 AN: 58004

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44964

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4388

European-Non Finnish (NFE) AF: 9.87e-7 AC: 1 AN: 1013070

Other (OTH) AF: 0.00 AC: 0 AN: 51016

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.061	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.022
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.82	T
M_CAP	Pathogenic	0.34	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	0.63	N
PhyloP100		1.5
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.20
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.17	T
Polyphen		0.76	P
Vest4		0.32
MutPred		0.48		Loss of MoRF binding (P = 0.0021)
MVP		0.56
MPC		0.53
ClinPred		0.49	T
GERP RS		3.8
PromoterAI		-0.0070	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.27
gMVP		0.42
Mutation Taster		=82/18	polymorphism

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: rs1221218095; hg19: chr17-48503708;