8-43056528-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

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. 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

Scores

2
1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.30
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

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

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FNTANM_002027.3 linkc.182C>T p.Pro61Leu missense_variant Exon 1 of 9 ENST00000302279.8 NP_002018.1 P49354-1
FNTANR_033698.2 linkn.206C>T non_coding_transcript_exon_variant Exon 1 of 8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FNTAENST00000302279.8 linkc.182C>T p.Pro61Leu missense_variant Exon 1 of 9 1 NM_002027.3 ENSP00000303423.3 P49354-1
ENSG00000254673ENST00000534420.1 linkn.71-2564C>T intron_variant Intron 1 of 5 4 ENSP00000435061.2 H0YE66
FNTAENST00000529687.5 linkc.-1033C>T upstream_gene_variant 2 ENSP00000473479.1 B3KVN2

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
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000831
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 25, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.182C>T (p.P61L) alteration is located in exon 1 (coding exon 1) of the FNTA gene. This alteration results from a C to T substitution at nucleotide position 182, causing the proline (P) at amino acid position 61 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
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
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.43
gMVP
0.34

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs945754308; hg19: chr8-42911671; API