12-51821159-G-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001384995.1(FIGNL2):​c.1255C>T​(p.Pro419Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000528 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: 0.0000053 (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.063889176).

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>T	p.Pro419Ser	missense	Exon 2 of 2	NP_001371924.1	A6NMB9
	FIGNL2	NM_001013690.5		c.1255C>T	p.Pro419Ser	missense	Exon 2 of 2	NP_001013712.4	A6NMB9
	FIGNL2	NM_001384996.1		c.1255C>T	p.Pro419Ser	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>T	p.Pro419Ser	missense	Exon 2 of 2	ENSP00000491257.1	A6NMB9
	FIGNL2	ENST00000938505.1		c.1255C>T	p.Pro419Ser	missense	Exon 2 of 2	ENSP00000608564.1
	FIGNL2	ENST00000948593.1		c.1255C>T	p.Pro419Ser	missense	Exon 2 of 2	ENSP00000618652.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000138 AC: 1 AN: 72218 AF XY: 0.0000238

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000759

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: 0.00000528 AC: 7 AN: 1324642 Hom.: 0 Cov.: 30 AF XY: 0.00000306 AC XY: 2 AN XY: 653062

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

American (AMR) AF: 0.0000409 AC: 1 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: 0.00000473 AC: 5 AN: 1056688

Other (OTH) AF: 0.0000181 AC: 1 AN: 55174

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_noAF	Benign	-0.53
CADD	Benign	14
DANN	Benign	0.92
DEOGEN2	Benign	0.0023	T
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.55	T
MetaRNN	Benign	0.064	T
MutationAssessor	Benign	-1.3	N
PhyloP100		0.50
PrimateAI	Pathogenic	0.86	D
Polyphen		0.0	B
GERP RS		1.8
Varity_R		0.070
gMVP		0.41

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;