3-14922536-C-A

Variant names:

• chr3-14922536-C-A
• rs149798859
• NM_152536.4:c.3795C>A

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.73
• Publications: 0 publications found

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]

LOC105376963 (HGNC:):

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.3795C>A	p.His1265Gln	missense	Exon 15 of 20	NP_689749.3
	FGD5	NM_001320276.2		c.3795C>A	p.His1265Gln	missense	Exon 15 of 19	NP_001307205.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGD5	ENST00000285046.10	TSL:1 MANE Select	c.3795C>A	p.His1265Gln	missense	Exon 15 of 20	ENSP00000285046.5	Q6ZNL6-1
	FGD5	ENST00000543601.5	TSL:1	c.3072C>A	p.His1024Gln	missense	Exon 15 of 19	ENSP00000445949.1	B7ZM68
	FGD5	ENST00000476851.1	TSL:1	n.1332C>A		non_coding_transcript_exon	Exon 12 of 17

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1429104 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 707612

African (AFR) AF: 0.00 AC: 0 AN: 32876

American (AMR) AF: 0.00 AC: 0 AN: 40020

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25540

East Asian (EAS) AF: 0.00 AC: 0 AN: 38094

South Asian (SAS) AF: 0.00 AC: 0 AN: 81466

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1095860

Other (OTH) AF: 0.00 AC: 0 AN: 59194

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Benign	-0.056	T
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	N
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Benign	0.92	L
PhyloP100		-2.7
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.44
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.63
MutPred		0.49		Gain of MoRF binding (P = 0.0792)
MVP		0.61
MPC		0.67
ClinPred		0.99	D
GERP RS		-8.8
Varity_R		0.27
gMVP		0.49
Mutation Taster		=58/42	polymorphism

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

Other links and lift over

dbSNP: rs149798859; hg19: chr3-14964043;