Genetic Variant NM_020369.3: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.

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.842-44C>G		intron	N/A	NP_065102.1	Q9NQT6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FSCN3	ENST00000265825.6	TSL:1 MANE Select	c.842-44C>G	intron	N/A	ENSP00000265825.5	Q9NQT6-1
FSCN3	ENST00000478821.1	TSL:5	c.440-44C>G	intron	N/A	ENSP00000473531.1	R4GN86
FSCN3	ENST00000469242.1	TSL:3	n.564-44C>G	intron	N/A

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over