Genetic Variant FIGNL1:p.Lys473Gln (chr7-50445871-T-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001287492.4(FIGNL1):c.1417A>C(p.Lys473Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000735 in 1,614,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00076 ( 0 hom. )

Consequence

FIGNL1
NM_001287492.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.02

Publications

4 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.819

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.1417A>C	p.Lys473Gln	missense	Exon 4 of 4	NP_001274421.1	Q6PIW4-1
FIGNL1	NM_001042762.5		c.1417A>C	p.Lys473Gln	missense	Exon 4 of 4	NP_001036227.1	Q6PIW4-1
FIGNL1	NM_001287493.3		c.1417A>C	p.Lys473Gln	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.1417A>C	p.Lys473Gln	missense	Exon 4 of 4	ENSP00000399997.1	Q6PIW4-1
FIGNL1	ENST00000356889.8	TSL:1	c.1417A>C	p.Lys473Gln	missense	Exon 4 of 4	ENSP00000349356.4	Q6PIW4-1
FIGNL1	ENST00000419119.1	TSL:1	c.1417A>C	p.Lys473Gln	missense	Exon 2 of 2	ENSP00000410811.1	Q6PIW4-1

Frequencies

GnomAD3 genomes

AF:

0.000506

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000848

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000852

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.000323

AC:

AN:

251096

AF XY:

0.000295

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.000608

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000759

AC:

1109

AN:

1461814

Hom.:

Cov.:

AF XY:

0.000683

AC XY:

497

AN XY:

727190

show subpopulations

African (AFR)

AF:

0.000239

AC:

AN:

33480

American (AMR)

AF:

0.0000671

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:

86258

European-Finnish (FIN)

AF:

0.000206

AC:

AN:

53346

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000940

AC:

1045

AN:

1112006

Other (OTH)

AF:

0.000695

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

133

200

266

333

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

160

200

<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

AF:

0.000506

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.000511

AC XY:

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41472

American (AMR)

AF:

0.000131

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5206

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000848

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000852

AC:

AN:

68038

Other (OTH)

AF:

0.000957

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000893

Hom.:

Bravo

AF:

0.000476

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.000346

AC:

EpiCase

AF:

0.000872

EpiControl

AF:

0.000474

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

Pathogenic

0.95

BayesDel_addAF

Uncertain

0.079

BayesDel_noAF

Pathogenic

0.27

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.66

Eigen

Pathogenic

0.88

Eigen_PC

Pathogenic

0.85

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

M_CAP

Uncertain

0.27

MetaRNN

Pathogenic

0.82

MetaSVM

Pathogenic

0.98

MutationAssessor

Uncertain

2.5

PhyloP100

8.0

PrimateAI

Pathogenic

0.88

PROVEAN

Uncertain

-3.9

REVEL

Pathogenic

0.84

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.78

MVP

0.99

MPC

0.17

ClinPred

0.25

GERP RS

6.0

Varity_R

0.93

gMVP

0.77

Mutation Taster

=25/75

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over