rs748048613

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001287492.4(FIGNL1):​c.1972A>G​(p.Lys658Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000176 in 1,595,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 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. K658Q) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 33)
Exomes š‘“: 0.000018 ( 0 hom. )

Consequence

FIGNL1
NM_001287492.4 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.25
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13202474).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FIGNL1NM_001287492.4 linkc.1972A>G p.Lys658Glu 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.1972A>G p.Lys658Glu missense_variant Exon 4 of 4 2 NM_001287492.4 ENSP00000399997.1 Q6PIW4-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152236
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000428
AC:
1
AN:
233422
Hom.:
0
AF XY:
0.00000793
AC XY:
1
AN XY:
126050
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000921
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000180
AC:
26
AN:
1442862
Hom.:
0
Cov.:
32
AF XY:
0.0000195
AC XY:
14
AN XY:
716828
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:
0.0000244
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000154
Gnomad4 OTH exome
AF:
0.0000504
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152236
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000283
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.092
BayesDel_addAF
Uncertain
0.042
T
BayesDel_noAF
Benign
-0.18
CADD
Benign
19
DANN
Benign
0.97
DEOGEN2
Benign
0.35
T;T;T;T;T;T;T;T
Eigen
Benign
-0.87
Eigen_PC
Benign
-0.72
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Benign
0.79
.;.;.;T;.;.;.;.
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.13
T;T;T;T;T;T;T;T
MetaSVM
Uncertain
-0.041
T
MutationAssessor
Benign
0.41
N;N;N;N;N;N;N;N
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-2.1
N;.;.;.;.;N;N;N
REVEL
Uncertain
0.33
Sift
Benign
0.15
T;.;.;.;.;T;T;T
Sift4G
Benign
0.27
T;T;T;T;T;T;T;T
Polyphen
0.0
B;B;B;B;B;B;B;B
Vest4
0.12
MutPred
0.29
Loss of ubiquitination at K658 (P = 0.0118);Loss of ubiquitination at K658 (P = 0.0118);Loss of ubiquitination at K658 (P = 0.0118);Loss of ubiquitination at K658 (P = 0.0118);Loss of ubiquitination at K658 (P = 0.0118);Loss of ubiquitination at K658 (P = 0.0118);Loss of ubiquitination at K658 (P = 0.0118);Loss of ubiquitination at K658 (P = 0.0118);
MVP
0.62
MPC
0.022
ClinPred
0.056
T
GERP RS
0.74
Varity_R
0.21
gMVP
0.66

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: rs748048613; hg19: chr7-50513014; API