5-447622-G-A

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC3	NM_007277.5	c.234G>A	p.Ser78Ser	synonymous_variant	Exon 3 of 13	ENST00000512944.6	NP_009208.2
EXOC3	XM_047416683.1	c.234G>A	p.Ser78Ser	synonymous_variant	Exon 3 of 7		XP_047272639.1
LOC124900930	XR_007058671.1	n.*230G>A		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOC3	ENST00000512944.6	c.234G>A	p.Ser78Ser	synonymous_variant	Exon 3 of 13	1	NM_007277.5	ENSP00000425587.1
EXOC3	ENST00000315013.9	c.234G>A	p.Ser78Ser	synonymous_variant	Exon 2 of 12	2		ENSP00000323377.5
EXOC3	ENST00000515601.6	n.234G>A		non_coding_transcript_exon_variant	Exon 3 of 12	5		ENSP00000424404.1
EXOC3	ENST00000508022.1	c.*28G>A		downstream_gene_variant		5		ENSP00000422596.1

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

GnomAD3 exomes AF: 0.00200 AC: 399 AN: 199208 Hom.: 6 AF XY: 0.00187 AC XY: 200 AN XY: 107204

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 SAS exome AF: 0.00320

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

Gnomad4 AFR exome AF: 0.000397

Gnomad4 AMR exome AF: 0.000620

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00880

Gnomad4 SAS exome AF: 0.00229

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000273

Gnomad4 OTH exome AF: 0.00602

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

Gnomad4 AFR AF: 0.00108

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0185

Gnomad4 SAS AF: 0.00518

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.000257 Hom.: 0

Bravo AF: 0.00133

Asia WGS AF: 0.0240 AC: 83 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 15, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.2
DANN	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

LitVar

Other links and lift over

dbSNP: rs180921423; hg19: chr5-447737;