chr8-43083128-G-A

Variant names:

• chr8-43083128-G-A
• rs1811057506
• NM_002027.3:c.793G>A

Variant summary

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

The NM_002027.3(FNTA):​c.793G>A​(p.Glu265Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000282 in 1,420,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.0000028 (0 hom.)
• Consequence: FNTA NM_002027.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.50
• Publications: 0 publications found

Genes affected

FNTA (HGNC:3782): (farnesyltransferase, CAAX box, alpha) Prenyltransferases can attach either a farnesyl group or a geranylgeranyl group in thioether linkage to the cysteine residue of proteins with a C-terminal CAAX box. CAAX geranylgeranyltransferase and CAAX farnesyltransferase are heterodimers that share the same alpha subunit but have different beta subunits. This gene encodes the alpha subunit of these transferases. Alternative splicing results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 11 and 13. [provided by RefSeq, May 2010]

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=0.20189482).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002027.3. 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
	FNTA	NM_002027.3	MANE Select	c.793G>A	p.Glu265Lys	missense	Exon 7 of 9	NP_002018.1	P49354-1
	FNTA	NR_033698.2		n.731G>A		non_coding_transcript_exon	Exon 6 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FNTA	ENST00000302279.8	TSL:1 MANE Select	c.793G>A	p.Glu265Lys	missense	Exon 7 of 9	ENSP00000303423.3	P49354-1
	FNTA	ENST00000529687.5	TSL:2	c.340G>A	p.Glu114Lys	missense	Exon 7 of 10	ENSP00000473479.1	B3KVN2
	FNTA	ENST00000526755.5	TSL:1	n.*3580G>A		non_coding_transcript_exon	Exon 6 of 8	ENSP00000437208.1	E9PK84

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000282 AC: 4 AN: 1420462 Hom.: 0 Cov.: 25 AF XY: 0.00000282 AC XY: 2 AN XY: 708308

African (AFR) AF: 0.00 AC: 0 AN: 31604

American (AMR) AF: 0.0000511 AC: 2 AN: 39156

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25554

East Asian (EAS) AF: 0.00 AC: 0 AN: 39300

South Asian (SAS) AF: 0.00 AC: 0 AN: 82010

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53108

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5506

European-Non Finnish (NFE) AF: 9.21e-7 AC: 1 AN: 1085338

Other (OTH) AF: 0.0000170 AC: 1 AN: 58886

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.27
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.047
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		3.5
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.043
Sift	Benign	0.28	T
Sift4G	Benign	0.34	T
Polyphen		0.10	B
Vest4		0.33
MutPred		0.45		Gain of ubiquitination at E265 (P = 0.03)
MVP		0.13
MPC		0.26
ClinPred		0.84	D
GERP RS		5.1
Varity_R		0.24
gMVP		0.33
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1811057506; hg19: chr8-42938271; COSMIC: COSV104403852; COSMIC: COSV104403852;