Genetic Variant FSCN3:c.842-44C>G (chr7-127596284-C-G) – 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.842-44C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 1,544,530 control chromosomes in the GnomAD database, including 12,411 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.

Frequency

Genomes: 𝑓 0.11 ( 1013 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11398 hom. )

Consequence

FSCN3
NM_020369.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0750

Publications

5 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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSCN3	NM_020369.3 link	c.842-44C>G		intron_variant	Intron 2 of 6	ENST00000265825.6	NP_065102.1	Q9NQT6-1A0A140VK18

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FSCN3	ENST00000265825.6 link	c.842-44C>G	intron_variant	Intron 2 of 6	1	NM_020369.3	ENSP00000265825.5	Q9NQT6-1
FSCN3	ENST00000478821.1 link	c.440-44C>G	intron_variant	Intron 2 of 2	5		ENSP00000473531.1	R4GN86
FSCN3	ENST00000469242.1 link	n.564-44C>G	intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.110

AC:

16779

AN:

151964

Hom.:

1013

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0800

Gnomad AMI

AF:

0.112

Gnomad AMR

AF:

0.0781

Gnomad ASJ

AF:

0.0973

Gnomad EAS

AF:

0.0619

Gnomad SAS

AF:

0.179

Gnomad FIN

AF:

0.182

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.125

Gnomad OTH

AF:

0.100

GnomAD2 exomes

AF:

0.118

AC:

29012

AN:

246632

AF XY:

0.122

show subpopulations

Gnomad AFR exome

AF:

0.0783

Gnomad AMR exome

AF:

0.0528

Gnomad ASJ exome

AF:

0.0945

Gnomad EAS exome

AF:

0.0608

Gnomad FIN exome

AF:

0.182

Gnomad NFE exome

AF:

0.125

Gnomad OTH exome

AF:

0.112

GnomAD4 exome

AF:

0.123

AC:

171562

AN:

1392448

Hom.:

11398

Cov.:

AF XY:

0.125

AC XY:

86620

AN XY:

694892

show subpopulations

African (AFR)

AF:

0.0804

AC:

2584

AN:

32130

American (AMR)

AF:

0.0570

AC:

2506

AN:

43980

Ashkenazi Jewish (ASJ)

AF:

0.0944

AC:

2390

AN:

25310

East Asian (EAS)

AF:

0.0541

AC:

2119

AN:

39176

South Asian (SAS)

AF:

0.173

AC:

14628

AN:

84318

European-Finnish (FIN)

AF:

0.181

AC:

9613

AN:

53004

Middle Eastern (MID)

AF:

0.0581

AC:

297

AN:

5114

European-Non Finnish (NFE)

AF:

0.125

AC:

130980

AN:

1051554

Other (OTH)

AF:

0.111

AC:

6445

AN:

57862

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

7078

14156

21233

28311

35389

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4670

9340

14010

18680

23350

<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:

0.110

AC:

16780

AN:

152082

Hom.:

1013

Cov.:

AF XY:

0.113

AC XY:

8388

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.0799

AC:

3316

AN:

41490

American (AMR)

AF:

0.0779

AC:

1191

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0973

AC:

337

AN:

3462

East Asian (EAS)

AF:

0.0617

AC:

319

AN:

5172

South Asian (SAS)

AF:

0.179

AC:

860

AN:

4812

European-Finnish (FIN)

AF:

0.182

AC:

1928

AN:

10568

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.125

AC:

8498

AN:

67972

Other (OTH)

AF:

0.0989

AC:

209

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

753

1506

2259

3012

3765

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

198

396

594

792

990

<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:

0.0731

Hom.:

112

Bravo

AF:

0.0983

Asia WGS

AF:

0.107

AC:

376

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.5

(source)

DANN

Benign

0.39

PhyloP100

0.075

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over