dbSNP rs3779536: FSCN3:p.Ala24Ser (chr7-127593923-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020369.3(FSCN3):c.70G>T(p.Ala24Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0423 in 1,606,384 control chromosomes in the GnomAD database, including 2,761 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.082 ( 885 hom., cov: 32)

Exomes 𝑓: 0.038 ( 1876 hom. )

Consequence

FSCN3
NM_020369.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.54

Publications

18 publications found

Variant links:

Genes affected

FSCN3 (HGNC:3961): (fascin actin-bundling protein 3) Predicted to enable actin filament binding activity. Predicted to be involved in actin filament bundle assembly; cell migration; and establishment or maintenance of cell polarity. Predicted to be located in cytoskeleton. Predicted to be active in several cellular components, including lamellipodium; microvillus; and ruffle. [provided by Alliance of Genome Resources, Apr 2022]

FSCN3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017133951).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020369.3. 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
	FSCN3	NM_020369.3	MANE Select	c.70G>T	p.Ala24Ser	missense	Exon 1 of 7	NP_065102.1	Q9NQT6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FSCN3	ENST00000265825.6	TSL:1 MANE Select	c.70G>T	p.Ala24Ser	missense	Exon 1 of 7	ENSP00000265825.5	Q9NQT6-1
FSCN3	ENST00000478328.1	TSL:1	n.544-1384G>T		intron	N/A
FSCN3	ENST00000478821.1	TSL:5	c.-259+171G>T		intron	N/A	ENSP00000473531.1	R4GN86

Frequencies

GnomAD3 genomes

AF:

0.0823

AC:

12522

AN:

152104

Hom.:

880

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.0572

Gnomad ASJ

AF:

0.0204

Gnomad EAS

AF:

0.0844

Gnomad SAS

AF:

0.104

Gnomad FIN

AF:

0.0620

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0306

Gnomad OTH

AF:

0.0684

GnomAD2 exomes

AF:

0.0599

AC:

14150

AN:

236206

AF XY:

0.0575

show subpopulations

Gnomad AFR exome

AF:

0.194

Gnomad AMR exome

AF:

0.0602

Gnomad ASJ exome

AF:

0.0220

Gnomad EAS exome

AF:

0.0800

Gnomad FIN exome

AF:

0.0599

Gnomad NFE exome

AF:

0.0306

Gnomad OTH exome

AF:

0.0453

GnomAD4 exome

AF:

0.0381

AC:

55434

AN:

1454162

Hom.:

1876

Cov.:

AF XY:

0.0393

AC XY:

28364

AN XY:

722296

show subpopulations

African (AFR)

AF:

0.186

AC:

6197

AN:

33394

American (AMR)

AF:

0.0605

AC:

2634

AN:

43546

Ashkenazi Jewish (ASJ)

AF:

0.0232

AC:

602

AN:

25944

East Asian (EAS)

AF:

0.0689

AC:

2725

AN:

39528

South Asian (SAS)

AF:

0.0968

AC:

8184

AN:

84502

European-Finnish (FIN)

AF:

0.0635

AC:

3356

AN:

52844

Middle Eastern (MID)

AF:

0.0232

AC:

134

AN:

5764

European-Non Finnish (NFE)

AF:

0.0261

AC:

28933

AN:

1108446

Other (OTH)

AF:

0.0443

AC:

2669

AN:

60194

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

2956

5911

8867

11822

14778

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1230

2460

3690

4920

6150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0824

AC:

12544

AN:

152222

Hom.:

885

Cov.:

AF XY:

0.0832

AC XY:

6191

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.187

AC:

7747

AN:

41504

American (AMR)

AF:

0.0571

AC:

874

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0204

AC:

AN:

3472

East Asian (EAS)

AF:

0.0840

AC:

434

AN:

5168

South Asian (SAS)

AF:

0.104

AC:

502

AN:

4826

European-Finnish (FIN)

AF:

0.0620

AC:

658

AN:

10610

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0307

AC:

2085

AN:

68014

Other (OTH)

AF:

0.0672

AC:

142

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

550

1100

1650

2200

2750

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

272

408

544

680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0437

Hom.:

1037

Bravo

AF:

0.0856

TwinsUK

AF:

0.0270

AC:

100

ALSPAC

AF:

0.0221

AC:

ESP6500AA

AF:

0.180

AC:

792

ESP6500EA

AF:

0.0251

AC:

216

ExAC

AF:

0.0614

AC:

7456

Asia WGS

AF:

0.0900

AC:

315

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0010

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.78

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

PhyloP100

5.5

PrimateAI

Uncertain

0.52

PROVEAN

Benign

0.16

REVEL

Benign

0.12

Sift

Benign

0.40

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.14

MPC

0.39

ClinPred

0.025

GERP RS

5.2

PromoterAI

-0.0069

Neutral

(source)

Varity_R

0.12

gMVP

0.53

Mutation Taster

=284/16

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over