rs1221218095

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr17-50426347-G-A
• chr17-50426347-G-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>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. 13/22 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
• 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=0.19248763).

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>A	p.Arg29Gln	missense	Exon 1 of 16	NP_079425.3
	ACSF2	NM_001288968.2		c.86G>A	p.Arg29Gln	missense	Exon 1 of 17	NP_001275897.1	Q96CM8-2
	ACSF2	NM_001288969.2		c.86G>A	p.Arg29Gln	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>A	p.Arg29Gln	missense	Exon 1 of 16	ENSP00000300441.4	Q96CM8-1
	ACSF2	ENST00000427954.6	TSL:2	c.86G>A	p.Arg29Gln	missense	Exon 1 of 17	ENSP00000401831.2	Q96CM8-2
	ACSF2	ENST00000942398.1		c.86G>A	p.Arg29Gln	missense	Exon 1 of 17	ENSP00000612457.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 95776 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: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

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

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: 58002

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: 0.00000494 AC: 5 AN: 1013070

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

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.021
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.15	N
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	0.63	N
PhyloP100		1.5
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.11
Sift	Benign	0.12	T
Sift4G	Benign	0.27	T
Polyphen		0.037	B
Vest4		0.29
MutPred		0.38		Loss of MoRF binding (P = 0.0464)
MVP		0.62
MPC		0.42
ClinPred		0.36	T
GERP RS		3.8
PromoterAI		-0.084	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.063
gMVP		0.32
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs1221218095; hg19: chr17-48503708;