NM_019053.6:c.390A>C

Variant names:

• chr10-92894998-A-C
• rs144456439
• NM_019053.6:c.390A>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_019053.6(EXOC6):​c.390A>C​(p.Glu130Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000685 in 1,609,782 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00071 (1 hom.)
• Consequence: EXOC6 NM_019053.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.58
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.049019128).

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.390A>C	p.Glu130Asp	missense	Exon 4 of 22	NP_061926.3
	EXOC6	NM_001319194.2		c.438A>C	p.Glu146Asp	missense	Exon 5 of 23	NP_001306123.1
	EXOC6	NM_001319195.2		c.390A>C	p.Glu130Asp	missense	Exon 4 of 22	NP_001306124.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC6	ENST00000260762.10	TSL:1 MANE Select	c.390A>C	p.Glu130Asp	missense	Exon 4 of 22	ENSP00000260762.6	Q8TAG9-1
	EXOC6	ENST00000443748.6	TSL:1	c.390A>C	p.Glu130Asp	missense	Exon 4 of 18	ENSP00000396206.2	E7EW84
	EXOC6	ENST00000371552.8	TSL:5	c.375A>C	p.Glu125Asp	missense	Exon 4 of 22	ENSP00000360607.4	Q8TAG9-2

Frequencies

GnomAD3 genomes AF: 0.000407 AC: 62 AN: 152228 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000853

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000284 AC: 71 AN: 250390 AF XY: 0.000273

Gnomad AFR exome AF: 0.000247

Gnomad AMR exome AF: 0.0000580

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000549

Gnomad OTH exome AF: 0.000492

GnomAD4 exome AF: 0.000714 AC: 1040 AN: 1457554 Hom.: 1 Cov.: 28 AF XY: 0.000731 AC XY: 530 AN XY: 725368

African (AFR) AF: 0.000150 AC: 5 AN: 33388

American (AMR) AF: 0.0000671 AC: 3 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39586

South Asian (SAS) AF: 0.00 AC: 0 AN: 86156

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.000911 AC: 1010 AN: 1108334

Other (OTH) AF: 0.000316 AC: 19 AN: 60220

GnomAD4 genome AF: 0.000407 AC: 62 AN: 152228 Hom.: 0 Cov.: 33 AF XY: 0.000457 AC XY: 34 AN XY: 74366

African (AFR) AF: 0.0000723 AC: 3 AN: 41472

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000853 AC: 58 AN: 68034

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.000787 Hom.: 0

Bravo AF: 0.000423

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000582 AC: 5

ExAC AF: 0.000280 AC: 34

EpiCase AF: 0.000873

EpiControl AF: 0.000652

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	0.10
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Benign	0.92
DEOGEN2	Benign	0.080	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.6
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.041
Sift	Benign	0.77	T
Sift4G	Benign	0.67	T
Polyphen		0.0030	B
Vest4		0.41
MVP		0.34
MPC		0.22
ClinPred		0.024	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.066
gMVP		0.35
Mutation Taster		=68/32	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: rs144456439; hg19: chr10-94654755;