12-95096472-T-C

Variant names:

• chr12-95096472-T-C
• rs12310399
• NM_018351.4:c.3498-1778A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018351.4. 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
	FGD6	NM_018351.4	MANE Select	c.3498-1778A>G		intron	N/A	NP_060821.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGD6	ENST00000343958.9	TSL:1 MANE Select	c.3498-1778A>G		intron	N/A	ENSP00000344446.4	Q6ZV73-1
	FGD6	ENST00000549499.1	TSL:1	c.3498-1778A>G		intron	N/A	ENSP00000449005.1	F8VY01
	FGD6	ENST00000451107.3	TSL:1	n.*893-1778A>G		intron	N/A	ENSP00000408291.3	F8VWT6

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

African (AFR) AF: 0.473 AC: 19618 AN: 41460

American (AMR) AF: 0.353 AC: 5395 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 979 AN: 3468

East Asian (EAS) AF: 0.326 AC: 1685 AN: 5170

South Asian (SAS) AF: 0.383 AC: 1844 AN: 4818

European-Finnish (FIN) AF: 0.262 AC: 2760 AN: 10550

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.364 AC: 24726 AN: 67962

Other (OTH) AF: 0.389 AC: 818 AN: 2104

Alfa AF: 0.372 Hom.: 19614

Bravo AF: 0.394

Asia WGS AF: 0.391 AC: 1360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.5
DANN	Benign	0.70
PhyloP100		-2.3
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: rs12310399; hg19: chr12-95490248;