NM_001384995.1:c.469G>A

Variant names:

• chr12-51821945-C-T
• rs1458987776
• NM_001384995.1:c.469G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001384995.1(FIGNL2):​c.469G>A​(p.Glu157Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 1,371,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. E157Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: FIGNL2 NM_001384995.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.59
• Publications: 0 publications found

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]

ENSG00000260473 (HGNC:):

ACMG classification

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, 0.782

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FIGNL2	NM_001384995.1	MANE Select	c.469G>A	p.Glu157Lys	missense	Exon 2 of 2	NP_001371924.1	A6NMB9
	FIGNL2	NM_001013690.5		c.469G>A	p.Glu157Lys	missense	Exon 2 of 2	NP_001013712.4	A6NMB9
	FIGNL2	NM_001384996.1		c.469G>A	p.Glu157Lys	missense	Exon 3 of 3	NP_001371925.1	A6NMB9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FIGNL2	ENST00000618634.3	TSL:5 MANE Select	c.469G>A	p.Glu157Lys	missense	Exon 2 of 2	ENSP00000491257.1	A6NMB9
	FIGNL2	ENST00000938505.1		c.469G>A	p.Glu157Lys	missense	Exon 2 of 2	ENSP00000608564.1
	FIGNL2	ENST00000948593.1		c.469G>A	p.Glu157Lys	missense	Exon 2 of 2	ENSP00000618652.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000158 AC: 2 AN: 126696 AF XY: 0.0000143

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000146 AC: 2 AN: 1371638 Hom.: 0 Cov.: 34 AF XY: 0.00000148 AC XY: 1 AN XY: 675186

African (AFR) AF: 0.00 AC: 0 AN: 29448

American (AMR) AF: 0.00 AC: 0 AN: 30822

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24390

East Asian (EAS) AF: 0.00 AC: 0 AN: 34014

South Asian (SAS) AF: 0.0000130 AC: 1 AN: 76972

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4024

European-Non Finnish (NFE) AF: 9.36e-7 AC: 1 AN: 1067870

Other (OTH) AF: 0.00 AC: 0 AN: 56492

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_noAF	Benign	-0.53
CADD	Uncertain	23
DANN	Benign	0.92
DEOGEN2	Benign	0.030	T
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.67	T
MetaRNN	Pathogenic	0.78	D
MutationAssessor	Uncertain	2.0	M
PhyloP100		7.6
PrimateAI	Pathogenic	0.96	D
Polyphen		1.0	D
GERP RS		4.4
Varity_R		0.18
gMVP		0.48

Splicing

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

Other links and lift over

dbSNP: rs1458987776; hg19: chr12-52215729;