chr8-43056528-C-T

Variant names:

• chr8-43056528-C-T
• rs945754308
• NM_002027.3:c.182C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_002027.3(FNTA):​c.182C>T​(p.Pro61Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000645 in 1,395,480 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 0.0000064 (0 hom.)
• Consequence: FNTA NM_002027.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.30
• 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]

ENSG00000254673 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.26651007).
• BS2: High AC in GnomAdExome4 at 9 AD gene.

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.182C>T	p.Pro61Leu	missense	Exon 1 of 9	NP_002018.1	P49354-1
	FNTA	NR_033698.2		n.206C>T		non_coding_transcript_exon	Exon 1 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FNTA	ENST00000302279.8	TSL:1 MANE Select	c.182C>T	p.Pro61Leu	missense	Exon 1 of 9	ENSP00000303423.3	P49354-1
	FNTA	ENST00000526755.5	TSL:1	n.182C>T		non_coding_transcript_exon	Exon 1 of 8	ENSP00000437208.1	E9PK84
	ENSG00000254673	ENST00000534420.1	TSL:4	n.71-2564C>T		intron	N/A	ENSP00000435061.2	H0YE66

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000645 AC: 9 AN: 1395480 Hom.: 0 Cov.: 30 AF XY: 0.00000723 AC XY: 5 AN XY: 691274

African (AFR) AF: 0.00 AC: 0 AN: 28746

American (AMR) AF: 0.00 AC: 0 AN: 36368

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24312

East Asian (EAS) AF: 0.00 AC: 0 AN: 33326

South Asian (SAS) AF: 0.00 AC: 0 AN: 77376

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49644

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5574

European-Non Finnish (NFE) AF: 0.00000831 AC: 9 AN: 1082450

Other (OTH) AF: 0.00 AC: 0 AN: 57684

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	0.15
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.16
Eigen_PC	Benign	0.020
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.81	T
M_CAP	Pathogenic	0.66	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.3
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.11
Sift	Benign	0.22	T
Sift4G	Benign	0.34	T
Polyphen		0.0040	B
Vest4		0.39
MutPred		0.51		Loss of sheet (P = 0.0104)
MVP		0.19
MPC		0.22
ClinPred		0.83	D
GERP RS		4.7
PromoterAI		0.00040	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.43
gMVP		0.34
Mutation Taster		=72/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs945754308; hg19: chr8-42911671;