7-127601926-C-T

Position:

• chr7-127601926-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020369.3(FSCN3):​c.*304C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0977 in 152,248 control chromosomes in the GnomAD database, including 992 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 0.098 (992 hom., cov: 32)
  • Exomes 𝑓: 0.050 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: FSCN3 NM_020369.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.370

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FSCN3	NM_020369.3	c.*304C>T		3_prime_UTR_variant	7/7	ENST00000265825.6	NP_065102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FSCN3	ENST00000265825.6	c.*304C>T		3_prime_UTR_variant	7/7	1	NM_020369.3	ENSP00000265825.5

Frequencies

GnomAD3 genomes AF: 0.0976 AC: 14853 AN: 152128 Hom.: 985 Cov.: 32

Gnomad AFR AF: 0.0232

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.0981

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.0989

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0500 AC: 3 AN: 60 Hom.: 1 Cov.: 0 AF XY: 0.0625 AC XY: 3 AN XY: 48

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.300

GnomAD4 genome AF: 0.0977 AC: 14873 AN: 152248 Hom.: 992 Cov.: 32 AF XY: 0.101 AC XY: 7545 AN XY: 74422

Gnomad4 AFR AF: 0.0231

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.0979

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.103

Alfa AF: 0.112 Hom.: 1509

Bravo AF: 0.102

Asia WGS AF: 0.150 AC: 520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.5
DANN	Benign	0.33

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

Other links and lift over

dbSNP: rs3824006; hg19: chr7-127241980;