rs4078292

chr9-92965176-C-T

Variant summary

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

The NM_001083536.2(FGD3):c.-217-10062C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 152,066 control chromosomes in the GnomAD database, including 8,339 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 0.32 (8339 hom., cov: 33)
• Consequence: FGD3 NM_001083536.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.437

Genes affected

FGD3 (HGNC:16027): (FYVE, RhoGEF and PH domain containing 3) Predicted to enable guanyl-nucleotide exchange factor activity and small GTPase binding activity. Predicted to be involved in several processes, including filopodium assembly; regulation of GTPase activity; and regulation of cell shape. Predicted to be located in Golgi apparatus; lamellipodium; and ruffle. Predicted to be active in cytoplasm. [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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGD3	NM_001083536.2	c.-217-10062C>T		intron_variant		ENST00000375482.8
FGD3	NM_001286993.2	c.-218+823C>T		intron_variant
FGD3	NM_001369951.1	c.-218+823C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGD3	ENST00000375482.8	c.-217-10062C>T		intron_variant		1	NM_001083536.2	P3
FGD3	ENST00000416701.6	c.-218+823C>T		intron_variant		2		A2
FGD3	ENST00000468206.6	c.-218+823C>T		intron_variant		2		P3

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49159 AN: 151948 Hom.: 8331 Cov.: 33

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.347

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.323 AC: 49183 AN: 152066 Hom.: 8339 Cov.: 33 AF XY: 0.321 AC XY: 23869 AN XY: 74316

Gnomad4 AFR AF: 0.392

Gnomad4 AMR AF: 0.395

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.346

Alfa AF: 0.295 Hom.: 3113

Bravo AF: 0.343

Asia WGS AF: 0.194 AC: 674 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	6.6
Dann	Benign	0.72

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: rs4078292; hg19: chr9-95727458;