Variant chr7-127595560-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_020369.3(FSCN3):c.398A>G(p.Tyr133Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,856 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

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.07

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 made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.773

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FSCN3	NM_020369.3 linkuse as main transcript	c.398A>G	p.Tyr133Cys	missense_variant	2/7	ENST00000265825.6	NP_065102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FSCN3	ENST00000265825.6 linkuse as main transcript	c.398A>G	p.Tyr133Cys	missense_variant	2/7	1	NM_020369.3	ENSP00000265825	P1	Q9NQT6-1
FSCN3	ENST00000478821.1 linkuse as main transcript	c.-5A>G		5_prime_UTR_variant	2/3	5		ENSP00000473531
FSCN3	ENST00000469242.1 linkuse as main transcript	n.120A>G		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461856

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727230

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.:

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 submitter

clinical testing

Ambry Genetics

Mar 25, 2022

The c.398A>G (p.Y133C) alteration is located in exon 2 (coding exon 2) of the FSCN3 gene. This alteration results from a A to G substitution at nucleotide position 398, causing the tyrosine (Y) at amino acid position 133 to be replaced by a cysteine (C). 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

0.20

BayesDel_addAF

Uncertain

0.089

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0061

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.83

M_CAP

Benign

0.018

MetaRNN

Pathogenic

0.77

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

0.94

D;D

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.47

REVEL

Benign

0.20

Sift

Benign

0.18

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.78

MutPred

0.62

Loss of sheet (P = 0.0817);

MVP

0.75

MPC

0.47

ClinPred

0.91

GERP RS

5.6

Varity_R

0.12

gMVP

0.38

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over