Genetic Variant FIGNL1:p.Ile497Val (chr7-50445799-T-C) – 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_001287492.4(FIGNL1):c.1489A>G(p.Ile497Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

FIGNL1
NM_001287492.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.27

Publications

0 publications found

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:

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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_001287492.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FIGNL1	NM_001287492.4	MANE Select	c.1489A>G	p.Ile497Val	missense	Exon 4 of 4	NP_001274421.1	Q6PIW4-1
FIGNL1	NM_001042762.5		c.1489A>G	p.Ile497Val	missense	Exon 4 of 4	NP_001036227.1	Q6PIW4-1
FIGNL1	NM_001287493.3		c.1489A>G	p.Ile497Val	missense	Exon 3 of 3	NP_001274422.1	Q6PIW4-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FIGNL1	ENST00000433017.6	TSL:2 MANE Select	c.1489A>G	p.Ile497Val	missense	Exon 4 of 4	ENSP00000399997.1	Q6PIW4-1
FIGNL1	ENST00000356889.8	TSL:1	c.1489A>G	p.Ile497Val	missense	Exon 4 of 4	ENSP00000349356.4	Q6PIW4-1
FIGNL1	ENST00000419119.1	TSL:1	c.1489A>G	p.Ile497Val	missense	Exon 2 of 2	ENSP00000410811.1	Q6PIW4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000796

AC:

AN:

251282

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1112008

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.080

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.050

MetaRNN

Uncertain

0.63

MetaSVM

Uncertain

0.58

MutationAssessor

Benign

1.4

PhyloP100

6.3

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.22

REVEL

Uncertain

0.57

Sift

Benign

0.31

Sift4G

Benign

0.41

Polyphen

0.96

Vest4

0.52

MutPred

0.81

Loss of sheet (P = 0.1398)

MVP

0.86

MPC

0.079

ClinPred

0.46

GERP RS

6.2

Varity_R

0.18

gMVP

0.49

Mutation Taster

=30/70

disease causing

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over