rs201166518

Variant names:

• chr2-163610163-C-T
• rs201166518
• NM_018086.4:c.1669G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018086.4(FIGN):​c.1669G>A​(p.Ala557Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000618 in 1,613,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00047 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00063 (0 hom.)
• Consequence: FIGN NM_018086.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.16
• Publications: 2 publications found

Genes affected

FIGN (HGNC:13285): (fidgetin, microtubule severing factor) Predicted to enable microtubule-severing ATPase activity. Predicted to be involved in cytoplasmic microtubule organization. Predicted to act upstream of or within locomotory behavior. Predicted to be located in nuclear matrix. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04472685).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018086.4. 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
	FIGN	NM_018086.4	MANE Select	c.1669G>A	p.Ala557Thr	missense	Exon 3 of 3	NP_060556.2	Q5HY92
	FIGN	NM_001321825.2		c.1636G>A	p.Ala546Thr	missense	Exon 2 of 2	NP_001308754.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FIGN	ENST00000333129.4	TSL:1 MANE Select	c.1669G>A	p.Ala557Thr	missense	Exon 3 of 3	ENSP00000333836.3	Q5HY92
	FIGN	ENST00000879555.1		c.1669G>A	p.Ala557Thr	missense	Exon 3 of 3	ENSP00000549614.1
	FIGN	ENST00000409634.5	TSL:5	c.26-16367G>A		intron	N/A	ENSP00000386768.1	B8ZZS6

Frequencies

GnomAD3 genomes AF: 0.000473 AC: 72 AN: 152096 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.000327

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: 0.000838

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000281 AC: 70 AN: 249230 AF XY: 0.000251

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000575

Gnomad OTH exome AF: 0.000496

GnomAD4 exome AF: 0.000633 AC: 925 AN: 1461856 Hom.: 0 Cov.: 38 AF XY: 0.000598 AC XY: 435 AN XY: 727226

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000799 AC: 888 AN: 1112000

Other (OTH) AF: 0.000497 AC: 30 AN: 60396

GnomAD4 genome AF: 0.000473 AC: 72 AN: 152096 Hom.: 0 Cov.: 32 AF XY: 0.000417 AC XY: 31 AN XY: 74288

African (AFR) AF: 0.000169 AC: 7 AN: 41410

American (AMR) AF: 0.000327 AC: 5 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000838 AC: 57 AN: 68010

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.000602 Hom.: 0

Bravo AF: 0.000461

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000606 AC: 5

ExAC AF: 0.000290 AC: 35

EpiCase AF: 0.000654

EpiControl AF: 0.000948

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	0.064
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.35	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.074	D
MetaRNN	Benign	0.045	T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Benign	-0.28	N
PhyloP100		2.2
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	0.50	N
REVEL	Benign	0.27
Sift	Benign	0.30	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.049
MVP		0.21
MPC		0.21
ClinPred		0.035	T
GERP RS		3.1
Varity_R		0.12
gMVP		0.51
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs201166518; hg19: chr2-164466673; COSMIC: COSV60766363; COSMIC: COSV60766363;