Genetic Variant EXOC3L4:p.Val160Met (chr14-103102201-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001077594.2(EXOC3L4):c.478G>A(p.Val160Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000346 in 1,445,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V160L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

EXOC3L4
NM_001077594.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.14

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22101146).

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.478G>A	p.Val160Met	missense	Exon 3 of 12	NP_001071062.1	Q17RC7
EXOC3L4	NM_001394941.1		c.478G>A	p.Val160Met	missense	Exon 4 of 13	NP_001381870.1	Q17RC7
EXOC3L4	NM_001394942.1		c.478G>A	p.Val160Met	missense	Exon 4 of 13	NP_001381871.1	Q17RC7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EXOC3L4	ENST00000688303.1	MANE Select	c.478G>A	p.Val160Met	missense	Exon 3 of 12	ENSP00000509130.1	Q17RC7
EXOC3L4	ENST00000380069.7	TSL:1	c.478G>A	p.Val160Met	missense	Exon 2 of 11	ENSP00000369409.3	Q17RC7
EXOC3L4	ENST00000687959.1		c.478G>A	p.Val160Met	missense	Exon 4 of 13	ENSP00000508483.1	Q17RC7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000462

AC:

AN:

216664

AF XY:

0.00000844

show subpopulations

Gnomad AFR exome

AF:

0.0000781

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000346

AC:

AN:

1445624

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

717906

show subpopulations

African (AFR)

AF:

0.000151

AC:

AN:

33032

American (AMR)

AF:

0.00

AC:

AN:

42954

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25872

East Asian (EAS)

AF:

0.00

AC:

AN:

38586

South Asian (SAS)

AF:

0.00

AC:

AN:

83656

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50970

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1105038

Other (OTH)

AF:

0.00

AC:

AN:

59770

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0039

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.81

M_CAP

Benign

0.010

MetaRNN

Benign

0.22

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

1.1

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.1

REVEL

Benign

0.060

Sift

Benign

0.15

Sift4G

Pathogenic

0.0

Polyphen

0.98

Vest4

0.26

MutPred

0.54

Gain of disorder (P = 0.0605)

MVP

0.072

MPC

0.19

ClinPred

0.49

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.084

gMVP

0.18

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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