NM_007277.5:c.536G>A

Variant names:

• chr5-453541-G-A
• rs1737715667
• NM_007277.5:c.536G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007277.5(EXOC3):​c.536G>A​(p.Ser179Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: EXOC3 NM_007277.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.71
• Publications: 0 publications found

Genes affected

EXOC3 (HGNC:30378): (exocyst complex component 3) The protein encoded by this gene is a component of the exocyst complex, a multiple protein complex essential for targeting exocytic vesicles to specific docking sites on the plasma membrane. Though best characterized in yeast, the component proteins and functions of exocyst complex have been demonstrated to be highly conserved in higher eukaryotes. At least eight components of the exocyst complex, including this protein, are found to interact with the actin cytoskeletal remodeling and vesicle transport machinery. The complex is also essential for the biogenesis of epithelial cell surface polarity. [provided by RefSeq, Jul 2008]

ACMG classification

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=0.13752508).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007277.5. 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
	EXOC3	NM_007277.5	MANE Select	c.536G>A	p.Ser179Asn	missense	Exon 4 of 13	NP_009208.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC3	ENST00000512944.6	TSL:1 MANE Select	c.536G>A	p.Ser179Asn	missense	Exon 4 of 13	ENSP00000425587.1	O60645
	EXOC3	ENST00000866266.1		c.536G>A	p.Ser179Asn	missense	Exon 4 of 13	ENSP00000536325.1
	EXOC3	ENST00000315013.9	TSL:2	c.536G>A	p.Ser179Asn	missense	Exon 3 of 12	ENSP00000323377.5	O60645

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000109 AC: 16 AN: 1461702 Hom.: 0 Cov.: 34 AF XY: 0.0000124 AC XY: 9 AN XY: 727130

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000144 AC: 16 AN: 1111870

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000468 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	20
DANN	Uncertain	0.99
Eigen	Benign	-0.17
Eigen_PC	Benign	0.026
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.98	T
PhyloP100		1.7
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.15	N
REVEL	Benign	0.051
Sift	Benign	0.048	D
Sift4G	Benign	0.068	T
Vest4		0.069
MVP		0.093
MPC		1.3
ClinPred		0.61	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.18
Mutation Taster		=94/6	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: rs1737715667; hg19: chr5-453656; COSMIC: COSV59269171; COSMIC: COSV59269171;