Genetic Variant FNTA:p.Asp110Gly (chr8-43064143-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002027.3(FNTA):c.329A>G(p.Asp110Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,752 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: 6.8e-7 ( 0 hom. )

Consequence

FNTA
NM_002027.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.23

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]

FNTA links:

ENSG00000254673 (HGNC:):

ENSG00000254673 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28860176).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FNTA	NM_002027.3 link	c.329A>G	p.Asp110Gly	missense_variant	Exon 3 of 9	ENST00000302279.8	NP_002018.1	P49354-1
FNTA	NR_033698.2 link	n.267A>G		non_coding_transcript_exon_variant	Exon 2 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FNTA	ENST00000302279.8 link	c.329A>G	p.Asp110Gly	missense_variant	Exon 3 of 9	1	NM_002027.3	ENSP00000303423.3	P49354-1
FNTA	ENST00000529687 link	c.-125A>G		5_prime_UTR_variant	Exon 3 of 10	2		ENSP00000473479.1	B3KVN2
ENSG00000254673	ENST00000534420.1 link	n.*103A>G		non_coding_transcript_exon_variant	Exon 3 of 6	4		ENSP00000435061.2	H0YE66
ENSG00000254673	ENST00000534420.1 link	n.*103A>G		3_prime_UTR_variant	Exon 3 of 6	4		ENSP00000435061.2	H0YE66

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251446

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461752

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 23, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.329A>G (p.D110G) alteration is located in exon 3 (coding exon 3) of the FNTA gene. This alteration results from a A to G substitution at nucleotide position 329, causing the aspartic acid (D) at amino acid position 110 to be replaced by a glycine (G). 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

Uncertain

0.39

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.099

T;.;T

Eigen

Benign

-0.068

Eigen_PC

Benign

0.14

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

D;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.29

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;.;.

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-2.0

N;N;N

REVEL

Uncertain

0.34

Sift

Benign

0.46

T;T;T

Sift4G

Benign

0.43

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.88

MutPred

0.32

Gain of MoRF binding (P = 0.0186);.;.;

MVP

0.57

MPC

0.29

ClinPred

0.42

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.46

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over