rs752523792

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr12-51821159-G-T
• chr12-51821159-G-A
• chr12-51821159-G-C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001384995.1(FIGNL2):​c.1255C>A​(p.Pro419Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000438 in 1,475,458 control chromosomes in the GnomAD database, including 2 homozygotes. 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: 𝑓 0.0024 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00021 (0 hom.)
• Consequence: FIGNL2 NM_001384995.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0055825114).
• BS2: High Homozygotes in GnomAd4 at 2 gene

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>A	p.Pro419Thr	missense	Exon 2 of 2	NP_001371924.1	A6NMB9
	FIGNL2	NM_001013690.5		c.1255C>A	p.Pro419Thr	missense	Exon 2 of 2	NP_001013712.4	A6NMB9
	FIGNL2	NM_001384996.1		c.1255C>A	p.Pro419Thr	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>A	p.Pro419Thr	missense	Exon 2 of 2	ENSP00000491257.1	A6NMB9
	FIGNL2	ENST00000938505.1		c.1255C>A	p.Pro419Thr	missense	Exon 2 of 2	ENSP00000608564.1
	FIGNL2	ENST00000948593.1		c.1255C>A	p.Pro419Thr	missense	Exon 2 of 2	ENSP00000618652.1

Frequencies

GnomAD3 genomes AF: 0.00240 AC: 362 AN: 150706 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00857

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000460

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00145

GnomAD2 exomes AF: 0.000208 AC: 15 AN: 72218 AF XY: 0.0000954

Gnomad AFR exome AF: 0.0127

Gnomad AMR exome AF: 0.000228

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: 0.000452

GnomAD4 exome AF: 0.000213 AC: 282 AN: 1324642 Hom.: 0 Cov.: 30 AF XY: 0.000190 AC XY: 124 AN XY: 653062

African (AFR) AF: 0.00924 AC: 242 AN: 26200

American (AMR) AF: 0.000286 AC: 7 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: 0.000232 AC: 1 AN: 4304

European-Non Finnish (NFE) AF: 0.00000757 AC: 8 AN: 1056688

Other (OTH) AF: 0.000435 AC: 24 AN: 55174

GnomAD4 genome AF: 0.00241 AC: 364 AN: 150816 Hom.: 2 Cov.: 32 AF XY: 0.00244 AC XY: 180 AN XY: 73698

African (AFR) AF: 0.00859 AC: 353 AN: 41098

American (AMR) AF: 0.000459 AC: 7 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 5028

South Asian (SAS) AF: 0.00 AC: 0 AN: 4786

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 270

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67560

Other (OTH) AF: 0.00143 AC: 3 AN: 2096

Alfa AF: 0.00137 Hom.: 0

Bravo AF: 0.00278

ExAC AF: 0.000168 AC: 5

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	0.073
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.86
DEOGEN2	Benign	0.0024	T
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.0056	T
MutationAssessor	Benign	-0.86	N
PhyloP100		0.50
PrimateAI	Pathogenic	0.87	D
Polyphen		0.0010	B
GERP RS		1.8
Varity_R		0.087
gMVP		0.44

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;