rs369533231

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2

The NM_152536.4(FGD5):​c.4025C>A​(p.Ser1342*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000684 in 1,461,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FGD5
NM_152536.4 stop_gained

Scores

3
3
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.96
Variant links:
Genes affected
FGD5 (HGNC:19117): (FYVE, RhoGEF and PH domain containing 5) 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. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
FGD5-AS1 (HGNC:40410): (FGD5 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 10 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FGD5NM_152536.4 linkc.4025C>A p.Ser1342* stop_gained Exon 17 of 20 ENST00000285046.10 NP_689749.3 Q6ZNL6-1A0A2X0SFF2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FGD5ENST00000285046.10 linkc.4025C>A p.Ser1342* stop_gained Exon 17 of 20 1 NM_152536.4 ENSP00000285046.5 Q6ZNL6-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461700
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
727132
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.62
D
BayesDel_noAF
Pathogenic
0.65
CADD
Pathogenic
42
DANN
Uncertain
0.99
Eigen
Uncertain
0.65
Eigen_PC
Uncertain
0.47
FATHMM_MKL
Pathogenic
0.98
D
Vest4
0.17
GERP RS
4.9

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-14965602; API