12-95109193-T-TA

Variant names:

• chr12-95109193-T-TA
• rs11382443
• NM_018351.4:c.3134-633_3134-632insT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_018351.4(FGD6):​c.3134-633_3134-632insT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (6996 hom., cov: 18)
• Consequence: FGD6 NM_018351.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.141
• Publications: 2 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGD6	NM_018351.4	c.3134-633_3134-632insT		intron_variant	Intron 9 of 20	ENST00000343958.9	NP_060821.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGD6	ENST00000343958.9	c.3134-633_3134-632insT		intron_variant	Intron 9 of 20	1	NM_018351.4	ENSP00000344446.4

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44899 AN: 151896 Hom.: 6985 Cov.: 18

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.296 AC: 44923 AN: 152018 Hom.: 6996 Cov.: 18 AF XY: 0.294 AC XY: 21868 AN XY: 74302

African (AFR) AF: 0.219 AC: 9063 AN: 41476

American (AMR) AF: 0.364 AC: 5558 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1342 AN: 3468

East Asian (EAS) AF: 0.411 AC: 2115 AN: 5152

South Asian (SAS) AF: 0.307 AC: 1483 AN: 4824

European-Finnish (FIN) AF: 0.237 AC: 2505 AN: 10568

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21943 AN: 67954

Other (OTH) AF: 0.323 AC: 682 AN: 2114

Alfa AF: 0.302 Hom.: 877

Bravo AF: 0.298

Asia WGS AF: 0.337 AC: 1174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.14
Mutation Taster		=29/71	disease causing

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: rs11382443; hg19: chr12-95502969;