12-95127594-C-T

Variant names:

• chr12-95127594-C-T
• rs11107909
• NM_018351.4:c.3082+7145G>A

Variant summary

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

The NM_018351.4(FGD6):​c.3082+7145G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0734 in 152,178 control chromosomes in the GnomAD database, including 507 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 0.073 (507 hom., cov: 33)
• Consequence: FGD6 NM_018351.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 6 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.143 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.3082+7145G>A		intron	N/A	NP_060821.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGD6	ENST00000343958.9	TSL:1 MANE Select	c.3082+7145G>A		intron	N/A	ENSP00000344446.4
	FGD6	ENST00000549499.1	TSL:1	c.3082+7145G>A		intron	N/A	ENSP00000449005.1
	FGD6	ENST00000451107.3	TSL:1	n.*477+7145G>A		intron	N/A	ENSP00000408291.3

Frequencies

GnomAD3 genomes AF: 0.0733 AC: 11142 AN: 152060 Hom.: 500 Cov.: 33

Gnomad AFR AF: 0.0384

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.0735

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.0987

Gnomad FIN AF: 0.0548

Gnomad MID AF: 0.0796

Gnomad NFE AF: 0.0735

Gnomad OTH AF: 0.0918

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

GnomAD4 genome AF: 0.0734 AC: 11163 AN: 152178 Hom.: 507 Cov.: 33 AF XY: 0.0745 AC XY: 5541 AN XY: 74402

African (AFR) AF: 0.0385 AC: 1598 AN: 41534

American (AMR) AF: 0.129 AC: 1975 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0735 AC: 255 AN: 3468

East Asian (EAS) AF: 0.152 AC: 787 AN: 5172

South Asian (SAS) AF: 0.0983 AC: 474 AN: 4820

European-Finnish (FIN) AF: 0.0548 AC: 581 AN: 10594

Middle Eastern (MID) AF: 0.0822 AC: 24 AN: 292

European-Non Finnish (NFE) AF: 0.0735 AC: 4999 AN: 68008

Other (OTH) AF: 0.0946 AC: 200 AN: 2114

Alfa AF: 0.0847 Hom.: 98

Bravo AF: 0.0796

Asia WGS AF: 0.164 AC: 569 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.90
DANN	Benign	0.64
PhyloP100		-1.4
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: rs11107909; hg19: chr12-95521370;