chr7-127595848-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_020369.3(FSCN3):​c.686A>T​(p.Asp229Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FSCN3
NM_020369.3 missense

Scores

6
7
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.73
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 made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.889

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FSCN3NM_020369.3 linkuse as main transcriptc.686A>T p.Asp229Val missense_variant 2/7 ENST00000265825.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FSCN3ENST00000265825.6 linkuse as main transcriptc.686A>T p.Asp229Val missense_variant 2/71 NM_020369.3 P1Q9NQT6-1
FSCN3ENST00000478821.1 linkuse as main transcriptc.284A>T p.Asp95Val missense_variant 2/35
FSCN3ENST00000469242.1 linkuse as main transcriptn.408A>T non_coding_transcript_exon_variant 1/23

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461506
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
727022
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 17, 2024The c.686A>T (p.D229V) alteration is located in exon 2 (coding exon 2) of the FSCN3 gene. This alteration results from a A to T substitution at nucleotide position 686, causing the aspartic acid (D) at amino acid position 229 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.58
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Uncertain
0.10
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.28
T;.
Eigen
Uncertain
0.55
Eigen_PC
Uncertain
0.58
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.81
T;T
M_CAP
Benign
0.049
D
MetaRNN
Pathogenic
0.89
D;D
MetaSVM
Benign
-0.62
T
MutationAssessor
Uncertain
2.7
M;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Benign
0.46
T
PROVEAN
Pathogenic
-7.5
D;.
REVEL
Uncertain
0.44
Sift
Pathogenic
0.0
D;.
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.96
D;.
Vest4
0.84
MutPred
0.77
Loss of sheet (P = 0.1398);.;
MVP
0.77
MPC
0.46
ClinPred
1.0
D
GERP RS
5.4
Varity_R
0.78
gMVP
0.77

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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.

Other links and lift over

dbSNP: rs755675031; hg19: chr7-127235902; API