dbSNP rs149798859: FGD5:p.His1265Gln (chr3-14922536-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152536.4(FGD5):c.3795C>A(p.His1265Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FGD5
NM_152536.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.73

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:

LOC105376963 (HGNC:):

LOC105376963 links:

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

FGD5-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGD5	NM_152536.4 link	c.3795C>A	p.His1265Gln	missense_variant	Exon 15 of 20	ENST00000285046.10	NP_689749.3	Q6ZNL6-1A0A2X0SFF2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGD5	ENST00000285046.10 link	c.3795C>A	p.His1265Gln	missense_variant	Exon 15 of 20	1	NM_152536.4	ENSP00000285046.5		Q6ZNL6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1429104

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

707612

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Benign

-0.056

BayesDel_noAF

Benign

-0.32

CADD

Benign

0.44

DANN

Benign

0.97

DEOGEN2

Benign

0.043

T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.81

T;D

M_CAP

Uncertain

0.17

MetaRNN

Uncertain

0.64

D;D

MetaSVM

Uncertain

-0.20

MutationAssessor

Benign

0.92

L;.

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-3.5

D;D

REVEL

Uncertain

0.44

Sift

Uncertain

0.017

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

1.0

D;D

Vest4

0.63

MutPred

0.49

Gain of MoRF binding (P = 0.0792);.;

MVP

0.61

MPC

0.67

ClinPred

0.99

GERP RS

-8.8

Varity_R

0.27

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over