3-14832287-T-C

Variant names:

• chr3-14832287-T-C
• rs7653784
• NM_152536.4:c.2525+10691T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152536.4. 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
	FGD5	NM_152536.4	MANE Select	c.2525+10691T>C		intron	N/A	NP_689749.3
	FGD5	NM_001320276.2		c.2525+10691T>C		intron	N/A	NP_001307205.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGD5	ENST00000285046.10	TSL:1 MANE Select	c.2525+10691T>C		intron	N/A	ENSP00000285046.5	Q6ZNL6-1
	FGD5	ENST00000543601.5	TSL:1	c.1802+10691T>C		intron	N/A	ENSP00000445949.1	B7ZM68
	FGD5	ENST00000969464.1		c.2525+10691T>C		intron	N/A	ENSP00000639523.1

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

African (AFR) AF: 0.882 AC: 36651 AN: 41544

American (AMR) AF: 0.703 AC: 10741 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 2346 AN: 3472

East Asian (EAS) AF: 0.656 AC: 3390 AN: 5168

South Asian (SAS) AF: 0.712 AC: 3429 AN: 4818

European-Finnish (FIN) AF: 0.783 AC: 8279 AN: 10576

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.758 AC: 51565 AN: 67990

Other (OTH) AF: 0.745 AC: 1573 AN: 2112

Alfa AF: 0.759 Hom.: 145301

Bravo AF: 0.778

Asia WGS AF: 0.710 AC: 2473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.076
DANN	Benign	0.52
PhyloP100		-1.0
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7653784;

hg19: chr3-14873794;