Genetic Variant NM_021807.4:c.244C>T (chr7-133275139-C-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_021807.4(EXOC4):c.244C>T(p.Arg82Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000827 in 1,450,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

EXOC4
NM_021807.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.74

Publications

1 publications found

Variant links:

Genes affected

EXOC4 (HGNC:30389): (exocyst complex component 4) 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. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

EXOC4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.878

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021807.4. 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
	EXOC4	NM_021807.4	MANE Select	c.244C>T	p.Arg82Cys	missense	Exon 2 of 18	NP_068579.3
	EXOC4	NM_001037126.2		c.244C>T	p.Arg82Cys	missense	Exon 2 of 10	NP_001032203.1	Q96A65-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EXOC4	ENST00000253861.5	TSL:1 MANE Select	c.244C>T	p.Arg82Cys	missense	Exon 2 of 18	ENSP00000253861.4	Q96A65-1
EXOC4	ENST00000462055.5	TSL:1	n.251C>T		non_coding_transcript_exon	Exon 2 of 9
EXOC4	ENST00000852803.1		c.244C>T	p.Arg82Cys	missense	Exon 2 of 19	ENSP00000522862.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000409

AC:

AN:

244324

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000899

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000827

AC:

AN:

1450648

Hom.:

Cov.:

AF XY:

0.00000416

AC XY:

AN XY:

721396

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33066

American (AMR)

AF:

0.00

AC:

AN:

42760

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25578

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39572

South Asian (SAS)

AF:

0.0000355

AC:

AN:

84504

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53060

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.00000633

AC:

AN:

1106604

Other (OTH)

AF:

0.00

AC:

AN:

59810

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

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

Pathogenic

0.76

BayesDel_addAF

Pathogenic

0.40

BayesDel_noAF

Pathogenic

0.34

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.73

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.014

MetaRNN

Pathogenic

0.88

MetaSVM

Benign

-0.41

MutationAssessor

Benign

1.8

PhyloP100

4.7

PrimateAI

Pathogenic

0.83

PROVEAN

Pathogenic

-4.7

REVEL

Uncertain

0.57

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.89

MutPred

0.61

Loss of MoRF binding (P = 0.0067)

MVP

0.91

MPC

0.72

ClinPred

1.0

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.56

gMVP

0.53

Mutation Taster

=61/39

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over