Genetic Variant FGD5:p.Pro1207Ser (chr3-14921967-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152536.4(FGD5):c.3619C>T(p.Pro1207Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000352 in 1,420,340 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: 0.0000035 ( 0 hom. )

Consequence

FGD5
NM_152536.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.83

Publications

0 publications found

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 links:

FGD5-AS1 (HGNC:40410): (FGD5 antisense RNA 1)

FGD5-AS1 links:

LOC105376963 (HGNC:):

LOC105376963 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2632804).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152536.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGD5	NM_152536.4	MANE Select	c.3619C>T	p.Pro1207Ser	missense	Exon 14 of 20	NP_689749.3
	FGD5	NM_001320276.2		c.3619C>T	p.Pro1207Ser	missense	Exon 14 of 19	NP_001307205.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FGD5	ENST00000285046.10	TSL:1 MANE Select	c.3619C>T	p.Pro1207Ser	missense	Exon 14 of 20	ENSP00000285046.5	Q6ZNL6-1
FGD5	ENST00000543601.5	TSL:1	c.2896C>T	p.Pro966Ser	missense	Exon 14 of 19	ENSP00000445949.1	B7ZM68
FGD5	ENST00000476851.1	TSL:1	n.1156C>T		non_coding_transcript_exon	Exon 11 of 17

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000540

AC:

AN:

185030

AF XY:

0.0000101

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000753

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000352

AC:

AN:

1420340

Hom.:

Cov.:

AF XY:

0.00000285

AC XY:

AN XY:

702508

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32538

American (AMR)

AF:

0.00

AC:

AN:

38616

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25462

East Asian (EAS)

AF:

0.000134

AC:

AN:

37192

South Asian (SAS)

AF:

0.00

AC:

AN:

80556

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5722

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1091024

Other (OTH)

AF:

0.00

AC:

AN:

58860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.097

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.75

M_CAP

Benign

0.019

MetaRNN

Benign

0.26

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

2.8

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.042

Sift

Benign

0.047

Sift4G

Benign

0.16

Polyphen

0.77

Vest4

0.36

MutPred

0.31

Gain of phosphorylation at P1207 (P = 0.035)

MVP

0.37

MPC

0.67

ClinPred

0.78

GERP RS

4.3

Varity_R

0.13

gMVP

0.12

Mutation Taster

=67/33

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over