7-127593864-C-T

Variant names:

• chr7-127593864-C-T
• rs946615240
• NM_020369.3:c.11C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020369.3(FSCN3):​c.11C>T​(p.Thr4Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000127 in 1,568,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: FSCN3 NM_020369.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.257
• Publications: 0 publications found

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]

ACMG classification

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 (MetaRNN=0.027630359).

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.11C>T	p.Thr4Ile	missense	Exon 1 of 7	NP_065102.1	Q9NQT6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSCN3	ENST00000265825.6	TSL:1 MANE Select	c.11C>T	p.Thr4Ile	missense	Exon 1 of 7	ENSP00000265825.5	Q9NQT6-1
	FSCN3	ENST00000478328.1	TSL:1	n.544-1443C>T		intron	N/A
	FSCN3	ENST00000478821.1	TSL:5	c.-259+112C>T		intron	N/A	ENSP00000473531.1	R4GN86

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152200 Hom.: 0 Cov.: 32

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: 7.06e-7 AC: 1 AN: 1416666 Hom.: 0 Cov.: 31 AF XY: 0.00000143 AC XY: 1 AN XY: 700196

African (AFR) AF: 0.00 AC: 0 AN: 32448

American (AMR) AF: 0.00 AC: 0 AN: 37616

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25298

East Asian (EAS) AF: 0.00 AC: 0 AN: 37262

South Asian (SAS) AF: 0.00 AC: 0 AN: 80434

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50498

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5720

European-Non Finnish (NFE) AF: 9.19e-7 AC: 1 AN: 1088578

Other (OTH) AF: 0.00 AC: 0 AN: 58812

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152200 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74348

⚠️ 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: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2094

⚠️ 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.

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.4
DANN	Benign	0.93
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.26
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.054
Sift	Benign	0.49	T
Sift4G	Benign	0.36	T
Polyphen		0.0	B
Vest4		0.036
MVP		0.13
MPC		0.079
ClinPred		0.046	T
GERP RS		-2.1
PromoterAI		-0.015	Neutral
Varity_R		0.031
gMVP		0.28
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs946615240; hg19: chr7-127233918;