GeneBe

7-127596284-C-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020369.3(FSCN3):​c.842-44C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000129 in 1,545,510 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

FSCN3
NM_020369.3 intron

Scores

2

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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FSCN3NM_020369.3 linkc.842-44C>A intron_variant Intron 2 of 6 ENST00000265825.6 NP_065102.1 Q9NQT6-1A0A140VK18

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FSCN3ENST00000265825.6 linkc.842-44C>A intron_variant Intron 2 of 6 1 NM_020369.3 ENSP00000265825.5 Q9NQT6-1
FSCN3ENST00000478821.1 linkc.440-44C>A intron_variant Intron 2 of 2 5 ENSP00000473531.1 R4GN86
FSCN3ENST00000469242.1 linkn.564-44C>A intron_variant Intron 1 of 1 3

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151980
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
7.18e-7
AC:
1
AN:
1393530
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
695412
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
32142
American (AMR)
AF:
0.00
AC:
0
AN:
43990
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25330
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39182
South Asian (SAS)
AF:
0.00
AC:
0
AN:
84356
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53026
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5122
European-Non Finnish (NFE)
AF:
9.50e-7
AC:
1
AN:
1052482
Other (OTH)
AF:
0.00
AC:
0
AN:
57900
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
151980
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74216
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
41372
American (AMR)
AF:
0.00
AC:
0
AN:
15268
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3464
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5184
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4818
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10568
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
67988
Other (OTH)
AF:
0.00
AC:
0
AN:
2092
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.275
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
112

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
2.0
DANN
Benign
0.50
PhyloP100
0.075

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

Other links and lift over

dbSNP: rs3735640; hg19: chr7-127236338; API