NM_020369.3:c.842-44C>G

Variant names:

• chr7-127596284-C-G
• rs3735640
• NM_020369.3:c.842-44C>G

Variant summary

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

The NM_020369.3(FSCN3):​c.842-44C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 1,544,530 control chromosomes in the GnomAD database, including 12,411 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 0.11 (1013 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11398 hom.)
• Consequence: FSCN3 NM_020369.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750
• Publications: 5 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 (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSCN3	NM_020369.3	c.842-44C>G		intron_variant	Intron 2 of 6	ENST00000265825.6	NP_065102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSCN3	ENST00000265825.6	c.842-44C>G		intron_variant	Intron 2 of 6	1	NM_020369.3	ENSP00000265825.5
FSCN3	ENST00000478821.1	c.440-44C>G		intron_variant	Intron 2 of 2	5		ENSP00000473531.1
FSCN3	ENST00000469242.1	n.564-44C>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16779 AN: 151964 Hom.: 1013 Cov.: 32

Gnomad AFR AF: 0.0800

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0781

Gnomad ASJ AF: 0.0973

Gnomad EAS AF: 0.0619

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.100

GnomAD2 exomes AF: 0.118 AC: 29012 AN: 246632 AF XY: 0.122

Gnomad AFR exome AF: 0.0783

Gnomad AMR exome AF: 0.0528

Gnomad ASJ exome AF: 0.0945

Gnomad EAS exome AF: 0.0608

Gnomad FIN exome AF: 0.182

Gnomad NFE exome AF: 0.125

Gnomad OTH exome AF: 0.112

GnomAD4 exome AF: 0.123 AC: 171562 AN: 1392448 Hom.: 11398 Cov.: 22 AF XY: 0.125 AC XY: 86620 AN XY: 694892

African (AFR) AF: 0.0804 AC: 2584 AN: 32130

American (AMR) AF: 0.0570 AC: 2506 AN: 43980

Ashkenazi Jewish (ASJ) AF: 0.0944 AC: 2390 AN: 25310

East Asian (EAS) AF: 0.0541 AC: 2119 AN: 39176

South Asian (SAS) AF: 0.173 AC: 14628 AN: 84318

European-Finnish (FIN) AF: 0.181 AC: 9613 AN: 53004

Middle Eastern (MID) AF: 0.0581 AC: 297 AN: 5114

European-Non Finnish (NFE) AF: 0.125 AC: 130980 AN: 1051554

Other (OTH) AF: 0.111 AC: 6445 AN: 57862

GnomAD4 genome AF: 0.110 AC: 16780 AN: 152082 Hom.: 1013 Cov.: 32 AF XY: 0.113 AC XY: 8388 AN XY: 74332

African (AFR) AF: 0.0799 AC: 3316 AN: 41490

American (AMR) AF: 0.0779 AC: 1191 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0973 AC: 337 AN: 3462

East Asian (EAS) AF: 0.0617 AC: 319 AN: 5172

South Asian (SAS) AF: 0.179 AC: 860 AN: 4812

European-Finnish (FIN) AF: 0.182 AC: 1928 AN: 10568

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8498 AN: 67972

Other (OTH) AF: 0.0989 AC: 209 AN: 2114

Alfa AF: 0.0731 Hom.: 112

Bravo AF: 0.0983

Asia WGS AF: 0.107 AC: 376 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.39
PhyloP100		0.075
Mutation Taster		=100/0	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: rs3735640; hg19: chr7-127236338; COSMIC: COSV50001112; COSMIC: COSV50001112;