chr12-95112847-A-G

Position:

• chr12-95112847-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
FGD6	NM_018351.4	c.3133+804T>C		intron_variant		ENST00000343958.9	NP_060821.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGD6	ENST00000343958.9	c.3133+804T>C		intron_variant		1	NM_018351.4	ENSP00000344446	P1

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

Gnomad4 AFR AF: 0.578

Gnomad4 AMR AF: 0.655

Gnomad4 ASJ AF: 0.722

Gnomad4 EAS AF: 0.678

Gnomad4 SAS AF: 0.635

Gnomad4 FIN AF: 0.740

Gnomad4 NFE AF: 0.636

Gnomad4 OTH AF: 0.628

Alfa AF: 0.635 Hom.: 14689

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

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: rs6538595; hg19: chr12-95506623;