Genetic Variant NM_001077594.2:c.388G>C (chr14-103100607-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001077594.2(EXOC3L4):c.388G>C(p.Glu130Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E130K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

EXOC3L4
NM_001077594.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0740

Publications

0 publications found

Variant links:

Genes affected

EXOC3L4 (HGNC:20120): (exocyst complex component 3 like 4) Predicted to enable SNARE binding activity. Predicted to be involved in exocyst localization and exocytosis. Predicted to be part of exocyst. [provided by Alliance of Genome Resources, Apr 2022]

EXOC3L4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.064677835).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077594.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EXOC3L4	NM_001077594.2	MANE Select	c.388G>C	p.Glu130Gln	missense	Exon 2 of 12	NP_001071062.1	Q17RC7
EXOC3L4	NM_001394941.1		c.388G>C	p.Glu130Gln	missense	Exon 3 of 13	NP_001381870.1	Q17RC7
EXOC3L4	NM_001394942.1		c.388G>C	p.Glu130Gln	missense	Exon 3 of 13	NP_001381871.1	Q17RC7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EXOC3L4	ENST00000688303.1	MANE Select	c.388G>C	p.Glu130Gln	missense	Exon 2 of 12	ENSP00000509130.1	Q17RC7
EXOC3L4	ENST00000380069.7	TSL:1	c.388G>C	p.Glu130Gln	missense	Exon 1 of 11	ENSP00000369409.3	Q17RC7
EXOC3L4	ENST00000687959.1		c.388G>C	p.Glu130Gln	missense	Exon 3 of 13	ENSP00000508483.1	Q17RC7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1449578

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

718708

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33284

American (AMR)

AF:

0.00

AC:

AN:

44022

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25886

East Asian (EAS)

AF:

0.00

AC:

AN:

39316

South Asian (SAS)

AF:

0.00

AC:

AN:

85546

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52708

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1103258

Other (OTH)

AF:

0.0000167

AC:

AN:

59842

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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.:

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

0.087

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

2.6

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0057

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.39

M_CAP

Benign

0.0065

MetaRNN

Benign

0.065

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.76

PhyloP100

-0.074

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.3

REVEL

Benign

0.018

Sift

Benign

0.22

Sift4G

Benign

0.52

Polyphen

0.024

Vest4

0.041

MutPred

0.27

Gain of methylation at K128 (P = 0.0997)

MVP

0.014

MPC

0.037

ClinPred

0.27

GERP RS

-4.1

PromoterAI

-0.026

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.077

gMVP

0.13

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over