chr7-127595349-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020369.3(FSCN3):​c.187G>A​(p.Val63Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

FSCN3
NM_020369.3 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.451
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0923163).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FSCN3NM_020369.3 linkuse as main transcriptc.187G>A p.Val63Met missense_variant 2/7 ENST00000265825.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FSCN3ENST00000265825.6 linkuse as main transcriptc.187G>A p.Val63Met missense_variant 2/71 NM_020369.3 P1Q9NQT6-1
FSCN3ENST00000478328.1 linkuse as main transcriptn.586G>A non_coding_transcript_exon_variant 2/21
FSCN3ENST00000478821.1 linkuse as main transcriptc.-216G>A 5_prime_UTR_variant 2/35
FSCN3ENST00000421705.1 linkuse as main transcriptc.*208G>A 3_prime_UTR_variant, NMD_transcript_variant 4/43

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152166
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.000288
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
GnomAD3 exomes
AF:
0.0000362
AC:
9
AN:
248614
Hom.:
0
AF XY:
0.0000446
AC XY:
6
AN XY:
134500
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000203
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000900
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000164
AC:
24
AN:
1461648
Hom.:
0
Cov.:
33
AF XY:
0.0000151
AC XY:
11
AN XY:
727114
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000201
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000117
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152166
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74314
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151
ExAC
AF:
0.0000412
AC:
5

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 GeneticsSep 16, 2021The c.187G>A (p.V63M) alteration is located in exon 2 (coding exon 2) of the FSCN3 gene. This alteration results from a G to A substitution at nucleotide position 187, causing the valine (V) at amino acid position 63 to be replaced by a methionine (M). 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
Benign
0.12
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
19
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0071
T
Eigen
Benign
-0.33
Eigen_PC
Benign
-0.29
FATHMM_MKL
Benign
0.30
N
LIST_S2
Benign
0.75
T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.092
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.3
M
MutationTaster
Benign
1.0
D;N
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.019
Sift
Benign
0.042
D
Sift4G
Uncertain
0.013
D
Polyphen
0.17
B
Vest4
0.31
MVP
0.20
MPC
0.14
ClinPred
0.072
T
GERP RS
2.6
Varity_R
0.072
gMVP
0.41

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs138368376; hg19: chr7-127235403; COSMIC: COSV50001332; COSMIC: COSV50001332; API