Genetic Variant FIGNL1:p.Gln493Arg (chr7-50445810-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001287492.4(FIGNL1):c.1478A>G(p.Gln493Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,614,240 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

FIGNL1
NM_001287492.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.02

Variant links:

Genes affected

FIGNL1 (HGNC:13286): (fidgetin like 1) This gene encodes a member of the AAA ATPase family of proteins. The encoded protein is recruited to sites of DNA damage where it plays a role in DNA double-strand break repair via homologous recombination. This protein has also been shown to localize to the centrosome and inhibit ciliogenesis, and may regulate the proliferation and differentiation of osteoblasts. [provided by RefSeq, Oct 2016]

FIGNL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FIGNL1	NM_001287492.4 link	c.1478A>G	p.Gln493Arg	missense_variant	Exon 4 of 4	ENST00000433017.6	NP_001274421.1	Q6PIW4-1B3KNH6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FIGNL1	ENST00000433017.6 link	c.1478A>G	p.Gln493Arg	missense_variant	Exon 4 of 4	2	NM_001287492.4	ENSP00000399997.1		Q6PIW4-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000576

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251246

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135800

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461868

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152372

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000577

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1478A>G (p.Q493R) alteration is located in exon 4 (coding exon 1) of the FIGNL1 gene. This alteration results from a A to G substitution at nucleotide position 1478, causing the glutamine (Q) at amino acid position 493 to be replaced by an arginine (R). 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

0.43

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Pathogenic

0.36

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.60

D;D;D;D;D;D;D;D

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

.;.;.;D;.;.;.;.

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.73

D;D;D;D;D;D;D;D

MetaSVM

Pathogenic

0.87

MutationAssessor

Benign

0.34

N;N;N;N;N;N;N;N

PrimateAI

Uncertain

0.79

PROVEAN

Uncertain

-3.9

D;.;.;.;.;D;D;D

REVEL

Pathogenic

0.79

Sift

Pathogenic

0.0

D;.;.;.;.;D;D;D

Sift4G

Uncertain

0.011

D;D;D;D;D;D;D;D

Polyphen

1.0

D;D;D;D;D;D;D;D

Vest4

0.71

MutPred

0.52

Gain of MoRF binding (P = 0.0364);Gain of MoRF binding (P = 0.0364);Gain of MoRF binding (P = 0.0364);Gain of MoRF binding (P = 0.0364);Gain of MoRF binding (P = 0.0364);Gain of MoRF binding (P = 0.0364);Gain of MoRF binding (P = 0.0364);Gain of MoRF binding (P = 0.0364);

MVP

0.92

MPC

0.16

ClinPred

0.76

GERP RS

6.0

Varity_R

0.83

gMVP

0.72

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