Variant 7-127593923-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FSCN3	NM_020369.3 linkuse as main transcript	c.70G>T	p.Ala24Ser	missense_variant	1/7	ENST00000265825.6	NP_065102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FSCN3	ENST00000265825.6 linkuse as main transcript	c.70G>T	p.Ala24Ser	missense_variant	1/7	1	NM_020369.3	ENSP00000265825	P1	Q9NQT6-1
FSCN3	ENST00000478328.1 linkuse as main transcript	n.544-1384G>T		intron_variant, non_coding_transcript_variant		1
FSCN3	ENST00000478821.1 linkuse as main transcript	c.-259+171G>T		intron_variant		5		ENSP00000473531
FSCN3	ENST00000421705.1 linkuse as main transcript	c.70G>T	p.Ala24Ser	missense_variant, NMD_transcript_variant	1/4	3		ENSP00000402472

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

GnomAD3 exomes

AF:

0.0599

AC:

14150

AN:

236206

Hom.:

679

AF XY:

0.0575

AC XY:

7317

AN XY:

127360

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 SAS exome

AF:

0.103

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

Gnomad4 AFR exome

AF:

0.186

Gnomad4 AMR exome

AF:

0.0605

Gnomad4 ASJ exome

AF:

0.0232

Gnomad4 EAS exome

AF:

0.0689

Gnomad4 SAS exome

AF:

0.0968

Gnomad4 FIN exome

AF:

0.0635

Gnomad4 NFE exome

AF:

0.0261

Gnomad4 OTH exome

AF:

0.0443

GnomAD4 genome

AF:

0.0824

AC:

12544

AN:

152222

Hom.:

885

Cov.:

AF XY:

0.0832

AC XY:

6191

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.187

Gnomad4 AMR

AF:

0.0571

Gnomad4 ASJ

AF:

0.0204

Gnomad4 EAS

AF:

0.0840

Gnomad4 SAS

AF:

0.104

Gnomad4 FIN

AF:

0.0620

Gnomad4 NFE

AF:

0.0307

Gnomad4 OTH

AF:

0.0672

Alfa

AF:

0.0382

Hom.:

420

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

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

MutationTaster

Benign

0.086

P;P

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

Varity_R

0.12

gMVP

0.53

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over