chr12-51821306-C-A

Variant names:

• chr12-51821306-C-A
• rs1185504478
• NM_001384995.1:c.1108G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001384995.1(FIGNL2):​c.1108G>T​(p.Val370Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000292 in 1,371,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 7/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: FIGNL2 NM_001384995.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.112
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.106125146).

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.1108G>T	p.Val370Leu	missense	Exon 2 of 2	NP_001371924.1	A6NMB9
	FIGNL2	NM_001013690.5		c.1108G>T	p.Val370Leu	missense	Exon 2 of 2	NP_001013712.4	A6NMB9
	FIGNL2	NM_001384996.1		c.1108G>T	p.Val370Leu	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.1108G>T	p.Val370Leu	missense	Exon 2 of 2	ENSP00000491257.1	A6NMB9
	FIGNL2	ENST00000938505.1		c.1108G>T	p.Val370Leu	missense	Exon 2 of 2	ENSP00000608564.1
	FIGNL2	ENST00000948593.1		c.1108G>T	p.Val370Leu	missense	Exon 2 of 2	ENSP00000618652.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000171 AC: 2 AN: 116986 AF XY: 0.0000154

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000118

Gnomad FIN exome AF: 0.000160

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000292 AC: 4 AN: 1371224 Hom.: 0 Cov.: 30 AF XY: 0.00000295 AC XY: 2 AN XY: 676894

African (AFR) AF: 0.00 AC: 0 AN: 29492

American (AMR) AF: 0.00 AC: 0 AN: 34152

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24448

East Asian (EAS) AF: 0.00 AC: 0 AN: 34062

South Asian (SAS) AF: 0.00 AC: 0 AN: 78100

European-Finnish (FIN) AF: 0.0000288 AC: 1 AN: 34736

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5632

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1073242

Other (OTH) AF: 0.0000523 AC: 3 AN: 57360

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.4
DANN	Benign	0.70
DEOGEN2	Benign	0.018	T
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.42	T
MetaRNN	Benign	0.11	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.11
PrimateAI	Pathogenic	0.91	D
Polyphen		0.069	B
GERP RS		2.0
Varity_R		0.038
gMVP		0.35

Splicing

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

Other links and lift over

dbSNP: rs1185504478; hg19: chr12-52215090;