Genetic Variant FSCN3:c.145-371C>T (chr7-127594936-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_020369.3(FSCN3):c.145-371C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0237 in 467,166 control chromosomes in the GnomAD database, including 174 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 0.020 ( 42 hom., cov: 32)

Exomes 𝑓: 0.026 ( 132 hom. )

Consequence

FSCN3
NM_020369.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.719

Publications

4 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=-0.87).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0195 (2969/152248) while in subpopulation NFE AF = 0.0316 (2152/68012). AF 95% confidence interval is 0.0305. There are 42 homozygotes in GnomAd4. There are 1382 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 42 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSCN3	NM_020369.3 link	c.145-371C>T		intron_variant	Intron 1 of 6	ENST00000265825.6	NP_065102.1	Q9NQT6-1A0A140VK18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSCN3	ENST00000265825.6 link	c.145-371C>T		intron_variant	Intron 1 of 6	1	NM_020369.3	ENSP00000265825.5		Q9NQT6-1

Frequencies

GnomAD3 genomes

AF:

0.0195

AC:

2970

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00570

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0114

Gnomad ASJ

AF:

0.0268

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0139

Gnomad FIN

AF:

0.0177

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0316

Gnomad OTH

AF:

0.0239

GnomAD4 exome

AF:

0.0257

AC:

8108

AN:

314918

Hom.:

132

Cov.:

AF XY:

0.0257

AC XY:

4531

AN XY:

176370

show subpopulations

African (AFR)

AF:

0.00506

AC:

AN:

8496

American (AMR)

AF:

0.00996

AC:

245

AN:

24600

Ashkenazi Jewish (ASJ)

AF:

0.0302

AC:

319

AN:

10560

East Asian (EAS)

AF:

0.000302

AC:

AN:

9934

South Asian (SAS)

AF:

0.0195

AC:

1144

AN:

58582

European-Finnish (FIN)

AF:

0.0229

AC:

591

AN:

25802

Middle Eastern (MID)

AF:

0.0210

AC:

AN:

1430

European-Non Finnish (NFE)

AF:

0.0332

AC:

5348

AN:

161154

Other (OTH)

AF:

0.0268

AC:

385

AN:

14360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

423

846

1268

1691

2114

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<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:

0.0195

AC:

2969

AN:

152248

Hom.:

Cov.:

AF XY:

0.0186

AC XY:

1382

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.00568

AC:

236

AN:

41540

American (AMR)

AF:

0.0113

AC:

173

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0268

AC:

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5188

South Asian (SAS)

AF:

0.0141

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0177

AC:

188

AN:

10608

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0316

AC:

2152

AN:

68012

Other (OTH)

AF:

0.0237

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

150

300

449

599

749

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<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:

0.0158

Hom.:

Bravo

AF:

0.0185

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.47

(source)

DANN

Benign

0.66

PhyloP100

-0.72

Mutation Taster

=100/0

polymorphism

(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