chr12-29270585-C-A

Variant names:

• chr12-29270585-C-A
• rs1303204479
• NM_001271783.2:c.136C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001271783.2(FAR2):​c.136C>A​(p.Pro46Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: FAR2 NM_001271783.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.55
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39645764).

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.136C>A	p.Pro46Thr	missense	Exon 2 of 12	NP_001258712.1	Q96K12-1
	FAR2	NM_018099.5		c.136C>A	p.Pro46Thr	missense	Exon 2 of 12	NP_060569.3
	FAR2	NM_001271784.2		c.-102-22715C>A		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.136C>A	p.Pro46Thr	missense	Exon 2 of 12	ENSP00000443291.2	Q96K12-1
	FAR2	ENST00000182377.8	TSL:1	c.136C>A	p.Pro46Thr	missense	Exon 2 of 12	ENSP00000182377.4	Q96K12-1
	FAR2	ENST00000946761.1		c.136C>A	p.Pro46Thr	missense	Exon 2 of 13	ENSP00000616820.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461726 Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3 AN XY: 727170

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111902

Other (OTH) AF: 0.00 AC: 0 AN: 60388

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	Benign	0.14
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		4.6
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-6.1	D
REVEL	Benign	0.17
Sift	Uncertain	0.010	D
Sift4G	Benign	0.11	T
Polyphen		0.79	P
Vest4		0.29
MutPred		0.54		Gain of catalytic residue at A48 (P = 0)
MVP		0.51
MPC		0.53
ClinPred		0.91	D
GERP RS		3.5
Varity_R		0.52
gMVP		0.50
Mutation Taster		=67/33	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: rs1303204479; hg19: chr12-29423518;