dbSNP rs945754308: FNTA:p.Pro61His (chr8-43056528-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_002027.3(FNTA):c.182C>A(p.Pro61His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,395,480 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P61L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

FNTA
NM_002027.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.30

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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>A	p.Pro61His	missense	Exon 1 of 9	NP_002018.1	P49354-1
	FNTA	NR_033698.2		n.206C>A		non_coding_transcript_exon	Exon 1 of 8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FNTA	ENST00000302279.8	TSL:1 MANE Select	c.182C>A	p.Pro61His	missense	Exon 1 of 9	ENSP00000303423.3	P49354-1
FNTA	ENST00000526755.5	TSL:1	n.182C>A		non_coding_transcript_exon	Exon 1 of 8	ENSP00000437208.1	E9PK84
ENSG00000254673	ENST00000534420.1	TSL:4	n.71-2564C>A		intron	N/A	ENSP00000435061.2	H0YE66

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1395480

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

691274

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

28746

American (AMR)

AF:

0.00

AC:

AN:

36368

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24312

East Asian (EAS)

AF:

0.00

AC:

AN:

33326

South Asian (SAS)

AF:

0.00

AC:

AN:

77376

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49644

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5574

European-Non Finnish (NFE)

AF:

0.00000185

AC:

AN:

1082450

Other (OTH)

AF:

0.00

AC:

AN:

57684

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0448430), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.350

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.042

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.70

M_CAP

Pathogenic

0.63

MetaRNN

Uncertain

0.47

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

PhyloP100

2.3

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.9

REVEL

Benign

0.088

Sift

Benign

0.048

Sift4G

Benign

0.10

Polyphen

0.86

Vest4

0.43

MutPred

0.42

Gain of catalytic residue at P61 (P = 0.0559)

MVP

0.18

MPC

0.44

ClinPred

0.88

GERP RS

4.7

PromoterAI

-0.016

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.52

gMVP

0.34

Mutation Taster

=69/31

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over