NM_018351.4:c.3133+804T>C

Variant names:

• chr12-95112847-A-G
• rs6538595
• NM_018351.4:c.3133+804T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018351.4(FGD6):​c.3133+804T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 152,058 control chromosomes in the GnomAD database, including 30,562 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 0.63 (30562 hom., cov: 31)
• Consequence: FGD6 NM_018351.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 10 publications found

Genes affected

FGD6 (HGNC:21740): (FYVE, RhoGEF and PH domain containing 6) 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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGD6	NM_018351.4	c.3133+804T>C		intron_variant	Intron 9 of 20	ENST00000343958.9	NP_060821.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGD6	ENST00000343958.9	c.3133+804T>C		intron_variant	Intron 9 of 20	1	NM_018351.4	ENSP00000344446.4

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95927 AN: 151940 Hom.: 30539 Cov.: 31

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.722

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.631 AC: 95981 AN: 152058 Hom.: 30562 Cov.: 31 AF XY: 0.637 AC XY: 47314 AN XY: 74322

African (AFR) AF: 0.578 AC: 23960 AN: 41470

American (AMR) AF: 0.655 AC: 10007 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.722 AC: 2506 AN: 3470

East Asian (EAS) AF: 0.678 AC: 3500 AN: 5160

South Asian (SAS) AF: 0.635 AC: 3066 AN: 4826

European-Finnish (FIN) AF: 0.740 AC: 7818 AN: 10572

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.636 AC: 43232 AN: 67966

Other (OTH) AF: 0.628 AC: 1329 AN: 2116

Alfa AF: 0.635 Hom.: 16405

Bravo AF: 0.623

Asia WGS AF: 0.610 AC: 2123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	5.7
DANN	Benign	0.90
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

Other links and lift over

dbSNP: rs6538595; hg19: chr12-95506623;