chr12-95172626-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The ENST00000343958.9(FGD6):c.2560G>A(p.Glu854Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
FGD6
ENST00000343958.9 missense
ENST00000343958.9 missense
Scores
8
11
Clinical Significance
Conservation
PhyloP100: 4.12
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2858432).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FGD6 | NM_018351.4 | c.2560G>A | p.Glu854Lys | missense_variant | 3/21 | ENST00000343958.9 | NP_060821.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FGD6 | ENST00000343958.9 | c.2560G>A | p.Glu854Lys | missense_variant | 3/21 | 1 | NM_018351.4 | ENSP00000344446 | P1 | |
FGD6 | ENST00000549499.1 | c.2560G>A | p.Glu854Lys | missense_variant | 3/16 | 1 | ENSP00000449005 | |||
FGD6 | ENST00000451107.3 | c.135G>A | p.Glu45= | synonymous_variant, NMD_transcript_variant | 2/20 | 1 | ENSP00000408291 | |||
FGD6 | ENST00000546711.5 | c.2560G>A | p.Glu854Lys | missense_variant | 3/19 | 5 | ENSP00000450342 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250416Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135340
GnomAD3 exomes
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GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1459152Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 725558
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
ExAC
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 29, 2023 | The c.2560G>A (p.E854K) alteration is located in exon 3 (coding exon 3) of the FGD6 gene. This alteration results from a G to A substitution at nucleotide position 2560, causing the glutamic acid (E) at amino acid position 854 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
P;.;.
Vest4
MutPred
Gain of ubiquitination at E854 (P = 0.0101);Gain of ubiquitination at E854 (P = 0.0101);Gain of ubiquitination at E854 (P = 0.0101);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at