5-447622-G-A

Variant names:

• chr5-447622-G-A
• rs180921423
• NM_007277.5:c.234G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_007277.5(EXOC3):​c.234G>A​(p.Ser78Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000732 in 1,584,356 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0014 (13 hom., cov: 33)
  • Exomes 𝑓: 0.00066 (30 hom.)
• Consequence: EXOC3 NM_007277.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.67
• Publications: 1 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]

LOC124900930 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 5-447622-G-A is Benign according to our data. Variant chr5-447622-G-A is described in ClinVar as Benign. ClinVar VariationId is 721259.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.67 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0014 (214/152334) while in subpopulation EAS AF = 0.0185 (96/5180). AF 95% confidence interval is 0.0155. There are 13 homozygotes in GnomAd4. There are 75 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

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.234G>A	p.Ser78Ser	synonymous	Exon 3 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.234G>A	p.Ser78Ser	synonymous	Exon 3 of 13	ENSP00000425587.1	O60645
	EXOC3	ENST00000866266.1		c.234G>A	p.Ser78Ser	synonymous	Exon 3 of 13	ENSP00000536325.1
	EXOC3	ENST00000315013.9	TSL:2	c.234G>A	p.Ser78Ser	synonymous	Exon 2 of 12	ENSP00000323377.5	O60645

Frequencies

GnomAD3 genomes AF: 0.00141 AC: 214 AN: 152216 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0185

Gnomad SAS AF: 0.00539

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00200 AC: 399 AN: 199208 AF XY: 0.00187

Gnomad AFR exome AF: 0.000529

Gnomad AMR exome AF: 0.000822

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0192

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000232

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.000660 AC: 945 AN: 1432022 Hom.: 30 Cov.: 31 AF XY: 0.000668 AC XY: 474 AN XY: 709636

African (AFR) AF: 0.000397 AC: 13 AN: 32720

American (AMR) AF: 0.000620 AC: 25 AN: 40354

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25606

East Asian (EAS) AF: 0.00880 AC: 333 AN: 37834

South Asian (SAS) AF: 0.00229 AC: 187 AN: 81816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.0000273 AC: 30 AN: 1097208

Other (OTH) AF: 0.00602 AC: 357 AN: 59324

GnomAD4 genome AF: 0.00140 AC: 214 AN: 152334 Hom.: 13 Cov.: 33 AF XY: 0.00101 AC XY: 75 AN XY: 74484

African (AFR) AF: 0.00108 AC: 45 AN: 41572

American (AMR) AF: 0.00255 AC: 39 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0185 AC: 96 AN: 5180

South Asian (SAS) AF: 0.00518 AC: 25 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68036

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.000257 Hom.: 0

Bravo AF: 0.00133

Asia WGS AF: 0.0240 AC: 83 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.2
DANN	Benign	0.83
PhyloP100		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs180921423; hg19: chr5-447737;