rs4078292

Variant names:

• chr9-92965176-C-T
• rs4078292
• NM_001083536.2:c.-217-10062C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001083536.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGD3	NM_001083536.2	MANE Select	c.-217-10062C>T		intron	N/A	NP_001077005.1	Q5JSP0-1
	FGD3	NM_001369951.1		c.-218+823C>T		intron	N/A	NP_001356880.1	Q5JSP0-1
	FGD3	NM_001286993.2		c.-218+823C>T		intron	N/A	NP_001273922.1	Q5JSP0-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGD3	ENST00000375482.8	TSL:1 MANE Select	c.-217-10062C>T		intron	N/A	ENSP00000364631.3	Q5JSP0-1
	FGD3	ENST00000941520.1		c.-218+823C>T		intron	N/A	ENSP00000611579.1
	FGD3	ENST00000468206.6	TSL:2	c.-218+823C>T		intron	N/A	ENSP00000496819.1	Q5JSP0-1

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

African (AFR) AF: 0.392 AC: 16254 AN: 41486

American (AMR) AF: 0.395 AC: 6043 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1316 AN: 3468

East Asian (EAS) AF: 0.127 AC: 656 AN: 5166

South Asian (SAS) AF: 0.197 AC: 950 AN: 4816

European-Finnish (FIN) AF: 0.276 AC: 2927 AN: 10590

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19740 AN: 67944

Other (OTH) AF: 0.346 AC: 730 AN: 2112

Alfa AF: 0.296 Hom.: 3463

Bravo AF: 0.343

Asia WGS AF: 0.194 AC: 674 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.6
DANN	Benign	0.72
PhyloP100		-0.44
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: rs4078292; hg19: chr9-95727458;