Genetic Variant NM_006544.4:c.1670A>G (chr14-57210005-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006544.4(EXOC5):c.1670A>G(p.Lys557Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,998 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

EXOC5
NM_006544.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.90

Publications

0 publications found

Variant links:

Genes affected

EXOC5 (HGNC:10696): (exocyst complex component 5) 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]

EXOC5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006544.4. 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
	EXOC5	NM_006544.4	MANE Select	c.1670A>G	p.Lys557Arg	missense	Exon 16 of 18	NP_006535.1	O00471

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EXOC5	ENST00000621441.5	TSL:1 MANE Select	c.1670A>G	p.Lys557Arg	missense	Exon 16 of 18	ENSP00000484855.1	O00471
EXOC5	ENST00000554011.5	TSL:1	n.1389A>G		non_coding_transcript_exon	Exon 6 of 8
EXOC5	ENST00000854286.1		c.1784A>G	p.Lys595Arg	missense	Exon 16 of 18	ENSP00000524345.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.91e-7

AC:

AN:

1446998

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719760

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33264

American (AMR)

AF:

0.0000227

AC:

AN:

44088

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25936

East Asian (EAS)

AF:

0.00

AC:

AN:

39440

South Asian (SAS)

AF:

0.00

AC:

AN:

84858

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53006

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5092

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1101540

Other (OTH)

AF:

0.00

AC:

AN:

59774

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Uncertain

0.055

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.023

MetaRNN

Uncertain

0.56

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.0

PhyloP100

7.9

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-2.3

REVEL

Benign

0.24

Sift

Pathogenic

0.0

Sift4G

Benign

0.10

Polyphen

0.92

Vest4

0.71

MutPred

0.44

Loss of methylation at K557 (P = 0.0159)

MVP

0.51

MPC

0.96

ClinPred

0.98

GERP RS

5.0

Varity_R

0.58

gMVP

0.35

Mutation Taster

=78/22

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over