3-14819120-G-A

Position:

• chr3-14819120-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_152536.4(FGD5):​c.49G>A​(p.Ala17Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FGD5 NM_152536.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.185

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.033682823).
• BP6: Variant 3-14819120-G-A is Benign according to our data. Variant chr3-14819120-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2540293.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGD5	NM_152536.4	c.49G>A	p.Ala17Thr	missense_variant	1/20	ENST00000285046.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGD5	ENST00000285046.10	c.49G>A	p.Ala17Thr	missense_variant	1/20	1	NM_152536.4	P1
FGD5	ENST00000543601.5	c.-675G>A		5_prime_UTR_variant	1/19	1
FGD5	ENST00000640506.1	c.178G>A	p.Ala60Thr	missense_variant	2/2	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 25, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	4.7
DANN	Benign	0.92
DEOGEN2	Benign	0.00088	.;T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.62	T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.034	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.11	.;N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.38	.;N
REVEL	Benign	0.087
Sift	Benign	0.81	.;T
Sift4G	Benign	0.81	.;T
Polyphen		0.0010	.;B
Vest4		0.027
MutPred		0.14		.;Gain of phosphorylation at A17 (P = 0.0341);
MVP		0.26
MPC		0.15
ClinPred		0.15	T
GERP RS		2.2
Varity_R		0.027
gMVP		0.090

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: chr3-14860627;