Genetic Variant NM_001384995.1:c.469G>C (chr12-51821945-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001384995.1(FIGNL2):c.469G>C(p.Glu157Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000919 in 1,523,678 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 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000080 ( 0 hom. )

Consequence

FIGNL2
NM_001384995.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.59

Publications

0 publications found

Variant links:

Genes affected

FIGNL2 (HGNC:13287): (fidgetin like 2) Predicted to enable microtubule-severing ATPase activity. Predicted to be involved in cytoplasmic microtubule organization. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

FIGNL2 links:

ENSG00000260473 (HGNC:):

ENSG00000260473 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.794

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384995.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FIGNL2	NM_001384995.1	MANE Select	c.469G>C	p.Glu157Gln	missense	Exon 2 of 2	NP_001371924.1	A6NMB9
FIGNL2	NM_001013690.5		c.469G>C	p.Glu157Gln	missense	Exon 2 of 2	NP_001013712.4	A6NMB9
FIGNL2	NM_001384996.1		c.469G>C	p.Glu157Gln	missense	Exon 3 of 3	NP_001371925.1	A6NMB9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FIGNL2	ENST00000618634.3	TSL:5 MANE Select	c.469G>C	p.Glu157Gln	missense	Exon 2 of 2	ENSP00000491257.1	A6NMB9
FIGNL2	ENST00000938505.1		c.469G>C	p.Glu157Gln	missense	Exon 2 of 2	ENSP00000608564.1
FIGNL2	ENST00000948593.1		c.469G>C	p.Glu157Gln	missense	Exon 2 of 2	ENSP00000618652.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152040

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000789

AC:

AN:

126696

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000213

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000802

AC:

AN:

1371638

Hom.:

Cov.:

AF XY:

0.00000889

AC XY:

AN XY:

675186

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29448

American (AMR)

AF:

0.00

AC:

AN:

30822

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24390

East Asian (EAS)

AF:

0.00

AC:

AN:

34014

South Asian (SAS)

AF:

0.00

AC:

AN:

76972

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4024

European-Non Finnish (NFE)

AF:

0.0000103

AC:

AN:

1067870

Other (OTH)

AF:

0.00

AC:

AN:

56492

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152040

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41436

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10574

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

67978

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000452

Hom.:

Bravo

AF:

0.0000189

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

Benign

0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.017

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.57

MetaRNN

Pathogenic

0.79

MutationAssessor

Uncertain

2.0

PhyloP100

7.6

PrimateAI

Pathogenic

0.94

Polyphen

1.0

GERP RS

4.4

Varity_R

0.17

gMVP

0.42

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over