rs888376656

Variant summary

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

The NM_001287492.4(FIGNL1):​c.1789G>T​(p.Val597Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,614,092 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V597I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FIGNL1
NM_001287492.4 missense

Scores

5
7
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.95
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]

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
FIGNL1NM_001287492.4 linkc.1789G>T p.Val597Leu 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
FIGNL1ENST00000433017.6 linkc.1789G>T p.Val597Leu missense_variant Exon 4 of 4 2 NM_001287492.4 ENSP00000399997.1 Q6PIW4-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152234
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461858
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727230
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152234
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.53
BayesDel_addAF
Pathogenic
0.35
D
BayesDel_noAF
Pathogenic
0.26
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.060
T;T;T;T;T;T;T;T
Eigen
Uncertain
0.38
Eigen_PC
Uncertain
0.35
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.55
.;.;.;T;.;.;.;.
M_CAP
Benign
0.083
D
MetaRNN
Uncertain
0.67
D;D;D;D;D;D;D;D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Pathogenic
2.9
M;M;M;M;M;M;M;M
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-1.6
N;.;.;.;.;N;N;N
REVEL
Uncertain
0.56
Sift
Benign
0.040
D;.;.;.;.;D;D;D
Sift4G
Benign
0.072
T;T;T;T;T;T;T;T
Polyphen
0.92
P;P;P;P;P;P;P;P
Vest4
0.55
MutPred
0.54
Gain of disorder (P = 0.1837);Gain of disorder (P = 0.1837);Gain of disorder (P = 0.1837);Gain of disorder (P = 0.1837);Gain of disorder (P = 0.1837);Gain of disorder (P = 0.1837);Gain of disorder (P = 0.1837);Gain of disorder (P = 0.1837);
MVP
0.95
MPC
0.023
ClinPred
0.52
D
GERP RS
6.2
Varity_R
0.42
gMVP
0.76

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.

Other links and lift over

dbSNP: rs888376656; hg19: chr7-50513197; API