Genetic Variant FIGNL2:p.Pro419Thr (chr12-51821159-G-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001384995.1(FIGNL2):c.1255C>A(p.Pro419Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000438 in 1,475,458 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 7/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0024 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

FIGNL2
NM_001384995.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.502

Variant links:

Genes affected

FIGNL2 (HGNC:13287): (fidgetin like 2) Predicted to enable microtubule-severing ATPase activity. Predicted to be involved in cytoplasmic microtubule organization. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

FIGNL2 links:

ENSG00000260473 (HGNC:):

ENSG00000260473 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0055825114).

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FIGNL2	NM_001384995.1 link	c.1255C>A	p.Pro419Thr	missense_variant	Exon 2 of 2	ENST00000618634.3	NP_001371924.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FIGNL2	ENST00000618634.3 link	c.1255C>A	p.Pro419Thr	missense_variant	Exon 2 of 2	5	NM_001384995.1	ENSP00000491257.1		A6NMB9
ENSG00000260473	ENST00000637934.1 link	n.177-2286G>T		intron_variant	Intron 2 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.00240

AC:

362

AN:

150706

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00857

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000460

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00145

GnomAD3 exomes

AF:

0.000208

AC:

AN:

72218

Hom.:

AF XY:

0.0000954

AC XY:

AN XY:

41950

show subpopulations

Gnomad AFR exome

AF:

0.0127

Gnomad AMR exome

AF:

0.000228

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:

0.000452

GnomAD4 exome

AF:

0.000213

AC:

282

AN:

1324642

Hom.:

Cov.:

AF XY:

0.000190

AC XY:

124

AN XY:

653062

show subpopulations

Gnomad4 AFR exome

AF:

0.00924

Gnomad4 AMR exome

AF:

0.000286

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:

0.00000757

Gnomad4 OTH exome

AF:

0.000435

GnomAD4 genome

AF:

0.00241

AC:

364

AN:

150816

Hom.:

Cov.:

AF XY:

0.00244

AC XY:

180

AN XY:

73698

show subpopulations

Gnomad4 AFR

AF:

0.00859

Gnomad4 AMR

AF:

0.000459

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.00137

Hom.:

Bravo

AF:

0.00278

ExAC

AF:

0.000168

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 17, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1255C>A (p.P419T) alteration is located in exon 2 (coding exon 1) of the FIGNL2 gene. This alteration results from a C to A substitution at nucleotide position 1255, causing the proline (P) at amino acid position 419 to be replaced by a threonine (T). 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

0.073

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.0024

T;T

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.52

.;T

MetaRNN

Benign

0.0056

T;T

MutationAssessor

Benign

-0.86

N;N

PrimateAI

Pathogenic

0.87

Polyphen

0.0010

B;B

GERP RS

1.8

Varity_R

0.087

gMVP

0.44

Splicing

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