Genetic Variant NM_001077594.2:c.278A>C (chr14-103100497-A-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.278A>C(p.Asp93Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000868 in 1,612,974 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000092 ( 0 hom. )

Consequence

EXOC3L4
NM_001077594.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.563

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:

Genome browser will be placed here

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=0.06401548).

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.278A>C	p.Asp93Ala	missense	Exon 2 of 12	NP_001071062.1	Q17RC7
EXOC3L4	NM_001394941.1		c.278A>C	p.Asp93Ala	missense	Exon 3 of 13	NP_001381870.1	Q17RC7
EXOC3L4	NM_001394942.1		c.278A>C	p.Asp93Ala	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.278A>C	p.Asp93Ala	missense	Exon 2 of 12	ENSP00000509130.1	Q17RC7
EXOC3L4	ENST00000380069.7	TSL:1	c.278A>C	p.Asp93Ala	missense	Exon 1 of 11	ENSP00000369409.3	Q17RC7
EXOC3L4	ENST00000687959.1		c.278A>C	p.Asp93Ala	missense	Exon 3 of 13	ENSP00000508483.1	Q17RC7

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000281

AC:

AN:

248832

AF XY:

0.0000296

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000871

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000357

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000917

AC:

134

AN:

1460870

Hom.:

Cov.:

AF XY:

0.0000908

AC XY:

AN XY:

726720

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000895

AC:

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86152

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52724

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000116

AC:

129

AN:

1111870

Other (OTH)

AF:

0.0000166

AC:

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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

AF:

0.0000394

AC:

AN:

152104

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41390

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000772

Hom.:

Bravo

AF:

0.0000567

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

0.077

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.44

CADD

Benign

6.5

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.0062

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.25

M_CAP

Benign

0.0083

MetaRNN

Benign

0.064

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

0.56

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.7

REVEL

Benign

0.057

Sift

Uncertain

0.026

Sift4G

Benign

0.13

Polyphen

0.0030

Vest4

0.079

MVP

0.014

MPC

0.041

ClinPred

0.083

GERP RS

3.1

PromoterAI

0.0031

Neutral

(source)

Varity_R

0.080

gMVP

0.15

Mutation Taster

=98/2

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over