chr7-127593923-G-T

Variant names:

• chr7-127593923-G-T
• rs3779536
• NM_020369.3:c.70G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020369.3(FSCN3):​c.70G>T​(p.Ala24Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0423 in 1,606,384 control chromosomes in the GnomAD database, including 2,761 homozygotes. 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 0.082 (885 hom., cov: 32)
  • Exomes 𝑓: 0.038 (1876 hom.)
• Consequence: FSCN3 NM_020369.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.54
• Publications: 18 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017133951).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSCN3	NM_020369.3	MANE Select	c.70G>T	p.Ala24Ser	missense	Exon 1 of 7	NP_065102.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FSCN3	ENST00000265825.6	TSL:1 MANE Select	c.70G>T	p.Ala24Ser	missense	Exon 1 of 7	ENSP00000265825.5
	FSCN3	ENST00000478328.1	TSL:1	n.544-1384G>T		intron	N/A
	FSCN3	ENST00000421705.1	TSL:3	n.70G>T		non_coding_transcript_exon	Exon 1 of 4	ENSP00000402472.1

Frequencies

GnomAD3 genomes AF: 0.0823 AC: 12522 AN: 152104 Hom.: 880 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0572

Gnomad ASJ AF: 0.0204

Gnomad EAS AF: 0.0844

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0620

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0306

Gnomad OTH AF: 0.0684

GnomAD2 exomes AF: 0.0599 AC: 14150 AN: 236206 AF XY: 0.0575

Gnomad AFR exome AF: 0.194

Gnomad AMR exome AF: 0.0602

Gnomad ASJ exome AF: 0.0220

Gnomad EAS exome AF: 0.0800

Gnomad FIN exome AF: 0.0599

Gnomad NFE exome AF: 0.0306

Gnomad OTH exome AF: 0.0453

GnomAD4 exome AF: 0.0381 AC: 55434 AN: 1454162 Hom.: 1876 Cov.: 32 AF XY: 0.0393 AC XY: 28364 AN XY: 722296

African (AFR) AF: 0.186 AC: 6197 AN: 33394

American (AMR) AF: 0.0605 AC: 2634 AN: 43546

Ashkenazi Jewish (ASJ) AF: 0.0232 AC: 602 AN: 25944

East Asian (EAS) AF: 0.0689 AC: 2725 AN: 39528

South Asian (SAS) AF: 0.0968 AC: 8184 AN: 84502

European-Finnish (FIN) AF: 0.0635 AC: 3356 AN: 52844

Middle Eastern (MID) AF: 0.0232 AC: 134 AN: 5764

European-Non Finnish (NFE) AF: 0.0261 AC: 28933 AN: 1108446

Other (OTH) AF: 0.0443 AC: 2669 AN: 60194

GnomAD4 genome AF: 0.0824 AC: 12544 AN: 152222 Hom.: 885 Cov.: 32 AF XY: 0.0832 AC XY: 6191 AN XY: 74432

African (AFR) AF: 0.187 AC: 7747 AN: 41504

American (AMR) AF: 0.0571 AC: 874 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0204 AC: 71 AN: 3472

East Asian (EAS) AF: 0.0840 AC: 434 AN: 5168

South Asian (SAS) AF: 0.104 AC: 502 AN: 4826

European-Finnish (FIN) AF: 0.0620 AC: 658 AN: 10610

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0307 AC: 2085 AN: 68014

Other (OTH) AF: 0.0672 AC: 142 AN: 2114

Alfa AF: 0.0437 Hom.: 1037

Bravo AF: 0.0856

TwinsUK AF: 0.0270 AC: 100

ALSPAC AF: 0.0221 AC: 85

ESP6500AA AF: 0.180 AC: 792

ESP6500EA AF: 0.0251 AC: 216

ExAC AF: 0.0614 AC: 7456

Asia WGS AF: 0.0900 AC: 315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0010	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.78	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		5.5
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.16	N
REVEL	Benign	0.12
Sift	Benign	0.40	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.14
MPC		0.39
ClinPred		0.025	T
GERP RS		5.2
PromoterAI		-0.0069	Neutral
Varity_R		0.12
gMVP		0.53
Mutation Taster		=284/16	polymorphism (auto)

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: rs3779536; hg19: chr7-127233977; COSMIC: COSV50000401; COSMIC: COSV50000401;