NM_001271783.2:c.139A>G

Variant names:

• chr12-29270588-A-G
• rs771178026
• NM_001271783.2:c.139A>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001271783.2(FAR2):​c.139A>G​(p.Lys47Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAR2 NM_001271783.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.69
• Publications: 0 publications found

Genes affected

FAR2 (HGNC:25531): (fatty acyl-CoA reductase 2) This gene belongs to the short chain dehydrogenase/reductase superfamily. It encodes a reductase enzyme involved in the first step of wax biosynthesis wherein fatty acids are converted to fatty alcohols. The encoded peroxisomal protein utilizes saturated fatty acids of 16 or 18 carbons as preferred substrates. Alternatively spliced transcript variants have been observed for this gene. Related pseudogenes have been identified on chromosomes 2, 14 and 22. [provided by RefSeq, Nov 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.897

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001271783.2. 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
	FAR2	NM_001271783.2	MANE Select	c.139A>G	p.Lys47Glu	missense	Exon 2 of 12	NP_001258712.1	Q96K12-1
	FAR2	NM_018099.5		c.139A>G	p.Lys47Glu	missense	Exon 2 of 12	NP_060569.3
	FAR2	NM_001271784.2		c.-102-22712A>G		intron	N/A	NP_001258713.1	Q96K12-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAR2	ENST00000536681.8	TSL:1 MANE Select	c.139A>G	p.Lys47Glu	missense	Exon 2 of 12	ENSP00000443291.2	Q96K12-1
	FAR2	ENST00000182377.8	TSL:1	c.139A>G	p.Lys47Glu	missense	Exon 2 of 12	ENSP00000182377.4	Q96K12-1
	FAR2	ENST00000946761.1		c.139A>G	p.Lys47Glu	missense	Exon 2 of 13	ENSP00000616820.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

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	Uncertain	0.54
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Pathogenic	0.76
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.071	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		8.7
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.55
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.81
MutPred		0.72		Gain of catalytic residue at A48 (P = 5e-04)
MVP		0.52
MPC		1.6
ClinPred		0.96	D
GERP RS		5.3
Varity_R		0.90
gMVP		0.82
Mutation Taster		=26/74	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs771178026; hg19: chr12-29423521;