Variant 2-163610163-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018086.4(FIGN):c.1669G>A(p.Ala557Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000618 in 1,613,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00063 ( 0 hom. )

Consequence

FIGN
NM_018086.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.16

Variant links:

Genes affected

FIGN (HGNC:13285): (fidgetin, microtubule severing factor) Predicted to enable microtubule-severing ATPase activity. Predicted to be involved in cytoplasmic microtubule organization. Predicted to act upstream of or within locomotory behavior. Predicted to be located in nuclear matrix. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

FIGN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04472685).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FIGN	NM_018086.4 linkuse as main transcript	c.1669G>A	p.Ala557Thr	missense_variant	3/3	ENST00000333129.4	NP_060556.2
FIGN	NM_001321825.2 linkuse as main transcript	c.1636G>A	p.Ala546Thr	missense_variant	2/2		NP_001308754.1
FIGN	XM_047444863.1 linkuse as main transcript	c.1747G>A	p.Ala583Thr	missense_variant	3/3		XP_047300819.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FIGN	ENST00000333129.4 linkuse as main transcript	c.1669G>A	p.Ala557Thr	missense_variant	3/3	1	NM_018086.4	ENSP00000333836	P1
FIGN	ENST00000409634.5 linkuse as main transcript	c.26-16367G>A		intron_variant		5		ENSP00000386768

Frequencies

GnomAD3 genomes

AF:

0.000473

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.000327

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:

0.000838

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000281

AC:

AN:

249230

Hom.:

AF XY:

0.000251

AC XY:

AN XY:

135196

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.0000290

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:

0.000575

Gnomad OTH exome

AF:

0.000496

GnomAD4 exome

AF:

0.000633

AC:

925

AN:

1461856

Hom.:

Cov.:

AF XY:

0.000598

AC XY:

435

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000894

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:

0.000799

Gnomad4 OTH exome

AF:

0.000497

GnomAD4 genome

AF:

0.000473

AC:

AN:

152096

Hom.:

Cov.:

AF XY:

0.000417

AC XY:

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000838

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000635

Hom.:

Bravo

AF:

0.000461

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000606

AC:

ExAC

AF:

0.000290

AC:

EpiCase

AF:

0.000654

EpiControl

AF:

0.000948

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 23, 2023

The c.1669G>A (p.A557T) alteration is located in exon 3 (coding exon 2) of the FIGN gene. This alteration results from a G to A substitution at nucleotide position 1669, causing the alanine (A) at amino acid position 557 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

0.064

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.35

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.074

MetaRNN

Benign

0.045

MetaSVM

Uncertain

-0.25

MutationAssessor

Benign

-0.28

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.65

PROVEAN

Benign

0.50

REVEL

Benign

0.27

Sift

Benign

0.30

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.049

MVP

0.21

MPC

0.21

ClinPred

0.035

GERP RS

3.1

Varity_R

0.12

gMVP

0.51

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