12-51821306-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

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=0.106125146).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FIGNL2	NM_001384995.1	c.1108G>T	p.Val370Leu	missense_variant	Exon 2 of 2	ENST00000618634.3	NP_001371924.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FIGNL2	ENST00000618634.3	c.1108G>T	p.Val370Leu	missense_variant	Exon 2 of 2	5	NM_001384995.1	ENSP00000491257.1
ENSG00000260473	ENST00000637934.1	n.177-2139C>A		intron_variant	Intron 2 of 4	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000171 AC: 2 AN: 116986 Hom.: 0 AF XY: 0.0000154 AC XY: 1 AN XY: 64936

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 SAS exome AF: 0.00

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

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: 0.00

Gnomad4 FIN exome AF: 0.0000288

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000523

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 01, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1108G>T (p.V370L) alteration is located in exon 2 (coding exon 1) of the FIGNL2 gene. This alteration results from a G to T substitution at nucleotide position 1108, causing the valine (V) at amino acid position 370 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.42	.;T
MetaRNN	Benign	0.11	T;T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Pathogenic	0.91	D
Polyphen		0.069	B;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

Publications

LitVar

Other links and lift over

dbSNP: rs1185504478; hg19: chr12-52215090;