rs10507047

Variant names:

• chr12-95210514-T-C
• rs10507047
• NM_018351.4:c.770A>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.770A>G​(p.Gln257Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 1,613,868 control chromosomes in the GnomAD database, including 10,259 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (989 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9270 hom.)
• Consequence: FGD6 NM_018351.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63
• Publications: 24 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 (MetaRNN=0.0033772886).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.239 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGD6	NM_018351.4	MANE Select	c.770A>G	p.Gln257Arg	missense	Exon 2 of 21	NP_060821.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGD6	ENST00000343958.9	TSL:1 MANE Select	c.770A>G	p.Gln257Arg	missense	Exon 2 of 21	ENSP00000344446.4
	FGD6	ENST00000549499.1	TSL:1	c.770A>G	p.Gln257Arg	missense	Exon 2 of 16	ENSP00000449005.1
	FGD6	ENST00000451107.3	TSL:1	n.16+6711A>G		intron	N/A	ENSP00000408291.3

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16614 AN: 152138 Hom.: 982 Cov.: 32

Gnomad AFR AF: 0.0982

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.0844

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.0912

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.0990

Gnomad OTH AF: 0.126

GnomAD2 exomes AF: 0.120 AC: 30208 AN: 250828 AF XY: 0.116

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.191

Gnomad ASJ exome AF: 0.0808

Gnomad EAS exome AF: 0.225

Gnomad FIN exome AF: 0.0918

Gnomad NFE exome AF: 0.100

Gnomad OTH exome AF: 0.111

GnomAD4 exome AF: 0.106 AC: 154750 AN: 1461612 Hom.: 9270 Cov.: 35 AF XY: 0.106 AC XY: 76722 AN XY: 727120

African (AFR) AF: 0.0955 AC: 3197 AN: 33460

American (AMR) AF: 0.186 AC: 8303 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.0771 AC: 2014 AN: 26120

East Asian (EAS) AF: 0.283 AC: 11215 AN: 39698

South Asian (SAS) AF: 0.0984 AC: 8480 AN: 86158

European-Finnish (FIN) AF: 0.0916 AC: 4891 AN: 53396

Middle Eastern (MID) AF: 0.0956 AC: 551 AN: 5766

European-Non Finnish (NFE) AF: 0.0984 AC: 109380 AN: 1111958

Other (OTH) AF: 0.111 AC: 6719 AN: 60390

GnomAD4 genome AF: 0.109 AC: 16643 AN: 152256 Hom.: 989 Cov.: 32 AF XY: 0.110 AC XY: 8159 AN XY: 74438

African (AFR) AF: 0.0983 AC: 4088 AN: 41570

American (AMR) AF: 0.145 AC: 2214 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0844 AC: 293 AN: 3470

East Asian (EAS) AF: 0.251 AC: 1296 AN: 5172

South Asian (SAS) AF: 0.0993 AC: 479 AN: 4824

European-Finnish (FIN) AF: 0.0912 AC: 967 AN: 10604

Middle Eastern (MID) AF: 0.0925 AC: 27 AN: 292

European-Non Finnish (NFE) AF: 0.0990 AC: 6733 AN: 68018

Other (OTH) AF: 0.129 AC: 273 AN: 2112

Alfa AF: 0.105 Hom.: 4388

Bravo AF: 0.116

TwinsUK AF: 0.0965 AC: 358

ALSPAC AF: 0.0913 AC: 352

ESP6500AA AF: 0.0958 AC: 422

ESP6500EA AF: 0.0972 AC: 836

ExAC AF: 0.117 AC: 14217

Asia WGS AF: 0.215 AC: 745 AN: 3478

EpiCase AF: 0.107

EpiControl AF: 0.101

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	8.2
DANN	Benign	0.97
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.38	T
MetaRNN	Benign	0.0034	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.6
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.14
Sift	Uncertain	0.029	D
Sift4G	Benign	0.078	T
Polyphen		0.48	P
Vest4		0.042
MPC		0.13
ClinPred		0.014	T
GERP RS		4.8
Varity_R		0.090
gMVP		0.11
Mutation Taster		=96/4	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: rs10507047; hg19: chr12-95604290; COSMIC: COSV59690373; COSMIC: COSV59690373;