3-14832287-T-C

Variant summary

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

The NM_152536.4(FGD5):c.2525+10691T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 152,160 control chromosomes in the GnomAD database, including 46,813 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 0.78 (46813 hom., cov: 32)
• Consequence: FGD5 NM_152536.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

Genes affected

FGD5 (HGNC:19117): (FYVE, RhoGEF and PH domain containing 5) 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. Located in plasma membrane. [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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGD5	NM_152536.4	c.2525+10691T>C		intron_variant		ENST00000285046.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGD5	ENST00000285046.10	c.2525+10691T>C		intron_variant		1	NM_152536.4	P1
FGD5	ENST00000543601.5	c.1802+10691T>C		intron_variant		1
FGD5	ENST00000457774.1	c.165+10691T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118643 AN: 152042 Hom.: 46764 Cov.: 32

Gnomad AFR AF: 0.882

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.713

Gnomad FIN AF: 0.783

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.748

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

GnomAD4 genome AF: 0.780 AC: 118747 AN: 152160 Hom.: 46813 Cov.: 32 AF XY: 0.779 AC XY: 57982 AN XY: 74386

Gnomad4 AFR AF: 0.882

Gnomad4 AMR AF: 0.703

Gnomad4 ASJ AF: 0.676

Gnomad4 EAS AF: 0.656

Gnomad4 SAS AF: 0.712

Gnomad4 FIN AF: 0.783

Gnomad4 NFE AF: 0.758

Gnomad4 OTH AF: 0.745

Alfa AF: 0.751 Hom.: 87674

Bravo AF: 0.778

Asia WGS AF: 0.710 AC: 2473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.076
Dann	Benign	0.52

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: rs7653784; hg19: chr3-14873794;