rs9309464

Variant names:

• chr2-72306834-A-G
• rs9309464
• NM_015189.3:c.2196+28113T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015189.3(EXOC6B):​c.2196+28113T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 152,096 control chromosomes in the GnomAD database, including 16,423 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (16423 hom., cov: 32)
• Consequence: EXOC6B NM_015189.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210
• Publications: 8 publications found

Genes affected

EXOC6B (HGNC:17085): (exocyst complex component 6B) This gene encodes a protein which is a part of the evolutionarily conserved exocyst, a multimeric protein complex necessary for exocytosis, which in turn, is crucial for cell growth, polarity and migration. Disruption of this gene may be associated with phenotypes exhibiting multiple symptoms including intellectual disability and developmental delay (DD). [provided by RefSeq, Jun 2016]

EXOC6B Gene-Disease associations (from GenCC):

• spondyloepimetaphyseal dysplasia with joint laxity, type 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
• spondyloepimetaphyseal dysplasia with joint laxity

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015189.3. 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
	EXOC6B	NM_015189.3	MANE Select	c.2196+28113T>C		intron	N/A	NP_056004.1	Q9Y2D4-1
	EXOC6B	NM_001321729.2		c.2196+28113T>C		intron	N/A	NP_001308658.1	A0A0U1RRB6
	EXOC6B	NM_001321731.2		c.2196+28113T>C		intron	N/A	NP_001308660.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC6B	ENST00000272427.11	TSL:1 MANE Select	c.2196+28113T>C		intron	N/A	ENSP00000272427.7	Q9Y2D4-1
	EXOC6B	ENST00000971151.1		c.2268+28113T>C		intron	N/A	ENSP00000641210.1
	EXOC6B	ENST00000971153.1		c.2229+28113T>C		intron	N/A	ENSP00000641212.1

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55456 AN: 151978 Hom.: 16371 Cov.: 32

Gnomad AFR AF: 0.822

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.0102

Gnomad SAS AF: 0.0944

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.315

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.365 AC: 55571 AN: 152096 Hom.: 16423 Cov.: 32 AF XY: 0.354 AC XY: 26328 AN XY: 74358

African (AFR) AF: 0.823 AC: 34124 AN: 41480

American (AMR) AF: 0.226 AC: 3448 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 653 AN: 3472

East Asian (EAS) AF: 0.0102 AC: 53 AN: 5186

South Asian (SAS) AF: 0.0930 AC: 449 AN: 4826

European-Finnish (FIN) AF: 0.191 AC: 2024 AN: 10580

Middle Eastern (MID) AF: 0.210 AC: 61 AN: 290

European-Non Finnish (NFE) AF: 0.205 AC: 13898 AN: 67952

Other (OTH) AF: 0.318 AC: 672 AN: 2114

Alfa AF: 0.253 Hom.: 18714

Bravo AF: 0.390

Asia WGS AF: 0.117 AC: 408 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.55
DANN	Benign	0.69
PhyloP100		-0.021
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs9309464;

hg19: chr2-72533963;