chr10-92848630-C-T

Variant names:

• chr10-92848630-C-T
• rs1847160686
• NM_019053.6:c.97C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_019053.6(EXOC6):​c.97C>T​(p.Leu33Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000786 in 1,272,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: EXOC6 NM_019053.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.21
• Publications: 0 publications found

Genes affected

EXOC6 (HGNC:23196): (exocyst complex component 6) The protein encoded by this gene is highly similar to the Saccharomyces cerevisiae SEC15 gene product, which is essential for vesicular traffic from the Golgi apparatus to the cell surface in yeast. It is one of the components of a multiprotein complex required for exocytosis. The 5' portion of this gene and two neighboring cytochrome p450 genes are included in a deletion that results in an autosomal-dominant form of nonsyndromic optic nerve aplasia (ONA). Alternative splicing and the use of alternative promoters results in multiple transcript variants. A paralogous gene encoding a similar protein is present on chromosome 2. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32502145).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019053.6. 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
	EXOC6	NM_019053.6	MANE Select	c.97C>T	p.Leu33Phe	missense	Exon 1 of 22	NP_061926.3
	EXOC6	NM_001319195.2		c.97C>T	p.Leu33Phe	missense	Exon 1 of 22	NP_001306124.1
	EXOC6	NM_001319200.2		c.97C>T	p.Leu33Phe	missense	Exon 1 of 18	NP_001306129.1	E7EW84

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC6	ENST00000260762.10	TSL:1 MANE Select	c.97C>T	p.Leu33Phe	missense	Exon 1 of 22	ENSP00000260762.6	Q8TAG9-1
	EXOC6	ENST00000443748.6	TSL:1	c.97C>T	p.Leu33Phe	missense	Exon 1 of 18	ENSP00000396206.2	E7EW84
	EXOC6	ENST00000371543.5	TSL:2	c.97C>T	p.Leu33Phe	missense	Exon 1 of 5	ENSP00000360598.1	B1AP46

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.86e-7 AC: 1 AN: 1272346 Hom.: 0 Cov.: 33 AF XY: 0.00000158 AC XY: 1 AN XY: 631680

African (AFR) AF: 0.00 AC: 0 AN: 25092

American (AMR) AF: 0.00 AC: 0 AN: 31076

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19728

East Asian (EAS) AF: 0.00 AC: 0 AN: 23066

South Asian (SAS) AF: 0.00 AC: 0 AN: 73464

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43736

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4970

European-Non Finnish (NFE) AF: 9.98e-7 AC: 1 AN: 1002394

Other (OTH) AF: 0.00 AC: 0 AN: 48820

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Pathogenic	0.74
BayesDel_addAF	Benign	-0.010	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Benign	0.96
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.045
FATHMM_MKL	Benign	0.13	N
LIST_S2	Uncertain	0.92	D
M_CAP	Pathogenic	0.53	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		3.2
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.19
Sift	Benign	0.67	T
Sift4G	Benign	0.50	T
Polyphen		0.62	P
Vest4		0.50
MutPred		0.54		Gain of phosphorylation at T32 (P = 0.1998)
MVP		0.45
MPC		0.28
ClinPred		0.71	D
GERP RS		2.9
PromoterAI		0.11	Neutral
Varity_R		0.12
gMVP		0.64
Mutation Taster		=56/44	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: rs1847160686; hg19: chr10-94608387;