rs12310399

chr12-95096472-T-Cchr12-95096472-T-G

Variant summary

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

The NM_018351.4(FGD6):c.3498-1778A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 152,006 control chromosomes in the GnomAD database, including 11,608 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 0.38 (11608 hom., cov: 32)
• Consequence: FGD6 NM_018351.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGD6	NM_018351.4	c.3498-1778A>G		intron_variant		ENST00000343958.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGD6	ENST00000343958.9	c.3498-1778A>G		intron_variant		1	NM_018351.4	P1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58402 AN: 151888 Hom.: 11577 Cov.: 32

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.385 AC: 58473 AN: 152006 Hom.: 11608 Cov.: 32 AF XY: 0.379 AC XY: 28128 AN XY: 74298

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.326

Gnomad4 SAS AF: 0.383

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.389

Alfa AF: 0.368 Hom.: 13870

Bravo AF: 0.394

Asia WGS AF: 0.391 AC: 1360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	3.5
Dann	Benign	0.70

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: rs12310399; hg19: chr12-95490248;