chr12-51821159-G-C

Variant names:

• chr12-51821159-G-C
• rs752523792
• NM_001384995.1:c.1255C>G

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.1255C>G​(p.Pro419Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000755 in 1,324,642 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. 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. P419T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: FIGNL2 NM_001384995.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.502
• 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=0.07567695).

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.1255C>G	p.Pro419Ala	missense	Exon 2 of 2	NP_001371924.1	A6NMB9
	FIGNL2	NM_001013690.5		c.1255C>G	p.Pro419Ala	missense	Exon 2 of 2	NP_001013712.4	A6NMB9
	FIGNL2	NM_001384996.1		c.1255C>G	p.Pro419Ala	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.1255C>G	p.Pro419Ala	missense	Exon 2 of 2	ENSP00000491257.1	A6NMB9
	FIGNL2	ENST00000938505.1		c.1255C>G	p.Pro419Ala	missense	Exon 2 of 2	ENSP00000608564.1
	FIGNL2	ENST00000948593.1		c.1255C>G	p.Pro419Ala	missense	Exon 2 of 2	ENSP00000618652.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.55e-7 AC: 1 AN: 1324642 Hom.: 0 Cov.: 30 AF XY: 0.00000153 AC XY: 1 AN XY: 653062

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26200

American (AMR) AF: 0.00 AC: 0 AN: 24440

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23114

East Asian (EAS) AF: 0.00 AC: 0 AN: 29298

South Asian (SAS) AF: 0.00 AC: 0 AN: 72508

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32916

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4304

European-Non Finnish (NFE) AF: 9.46e-7 AC: 1 AN: 1056688

Other (OTH) AF: 0.00 AC: 0 AN: 55174

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_noAF	Benign	-0.55
CADD	Benign	16
DANN	Benign	0.73
DEOGEN2	Benign	0.0052	T
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.076	T
MutationAssessor	Benign	-0.92	N
PhyloP100		0.50
PrimateAI	Pathogenic	0.87	D
Polyphen		0.0	B
GERP RS		1.8
Varity_R		0.067
gMVP		0.35

Splicing

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

Other links and lift over

dbSNP: rs752523792; hg19: chr12-52214943;