dbSNP rs748048613: FIGNL1:p.Lys658Glu (chr7-50445316-T-C) – ACMG Classification: Uncertain_significance (0 pts)

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: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

FIGNL1
NM_001287492.4 missense

Scores

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]

FIGNL1 links:

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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
FIGNL1	NM_001287492.4 link	c.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
FIGNL1	ENST00000433017.6 link	c.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:

AN:

152236

Hom.:

Cov.:

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:

AN:

233422

Hom.:

AF XY:

0.00000793

AC XY:

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:

AN:

1442862

Hom.:

Cov.:

AF XY:

0.0000195

AC XY:

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:

AN:

152236

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

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.:

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

BayesDel_noAF

Benign

-0.18

CADD

Benign

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

LIST_S2

Benign

0.79

.;.;.;T;.;.;.;.

M_CAP

Benign

0.030

MetaRNN

Benign

0.13

T;T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.041

MutationAssessor

Benign

0.41

N;N;N;N;N;N;N;N

PrimateAI

Benign

0.32

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over