7-127594936-C-T

Variant names:

• chr7-127594936-C-T
• rs806213
• NM_020369.3:c.145-371C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_020369.3(FSCN3):​c.145-371C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0237 in 467,166 control chromosomes in the GnomAD database, including 174 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 0.020 (42 hom., cov: 32)
  • Exomes 𝑓: 0.026 (132 hom.)
• Consequence: FSCN3 NM_020369.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.719

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=-0.87).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0195 (2969/152248) while in subpopulation NFE AF= 0.0316 (2152/68012). AF 95% confidence interval is 0.0305. There are 42 homozygotes in gnomad4. There are 1382 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 42 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSCN3	NM_020369.3	c.145-371C>T		intron_variant	Intron 1 of 6	ENST00000265825.6	NP_065102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FSCN3	ENST00000265825.6	c.145-371C>T		intron_variant	Intron 1 of 6	1	NM_020369.3	ENSP00000265825.5

Frequencies

GnomAD3 genomes AF: 0.0195 AC: 2970 AN: 152130 Hom.: 42 Cov.: 32

Gnomad AFR AF: 0.00570

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0114

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0139

Gnomad FIN AF: 0.0177

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0316

Gnomad OTH AF: 0.0239

GnomAD4 exome AF: 0.0257 AC: 8108 AN: 314918 Hom.: 132 Cov.: 0 AF XY: 0.0257 AC XY: 4531 AN XY: 176370

Gnomad4 AFR exome AF: 0.00506

Gnomad4 AMR exome AF: 0.00996

Gnomad4 ASJ exome AF: 0.0302

Gnomad4 EAS exome AF: 0.000302

Gnomad4 SAS exome AF: 0.0195

Gnomad4 FIN exome AF: 0.0229

Gnomad4 NFE exome AF: 0.0332

Gnomad4 OTH exome AF: 0.0268

GnomAD4 genome AF: 0.0195 AC: 2969 AN: 152248 Hom.: 42 Cov.: 32 AF XY: 0.0186 AC XY: 1382 AN XY: 74426

Gnomad4 AFR AF: 0.00568

Gnomad4 AMR AF: 0.0113

Gnomad4 ASJ AF: 0.0268

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0141

Gnomad4 FIN AF: 0.0177

Gnomad4 NFE AF: 0.0316

Gnomad4 OTH AF: 0.0237

Alfa AF: 0.0158 Hom.: 6

Bravo AF: 0.0185

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.47
DANN	Benign	0.66

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: rs806213; hg19: chr7-127234990;