Genetic Variant EXOC3L1:c.-8+99C>T (chr16-67189872-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_178516.4(EXOC3L1):c.-8+99C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00583 in 611,004 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.017 ( 83 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 24 hom. )

Consequence

EXOC3L1
NM_178516.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.125

Publications

3 publications found

Variant links:

Genes affected

EXOC3L1 (HGNC:27540): (exocyst complex component 3 like 1) Predicted to enable SNARE binding activity. Predicted to be involved in exocyst localization; exocytosis; and peptide hormone secretion. Predicted to be located in secretory granule. Predicted to be part of exocyst. [provided by Alliance of Genome Resources, Apr 2022]

EXOC3L1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0558 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178516.4. 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
	EXOC3L1	NM_178516.4	MANE Select	c.-8+99C>T		intron	N/A	NP_848611.2	Q86VI1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EXOC3L1	ENST00000314586.11	TSL:2 MANE Select	c.-8+99C>T	intron	N/A	ENSP00000325674.6	Q86VI1
EXOC3L1	ENST00000925362.1		c.-196C>T	5_prime_UTR_premature_start_codon_gain	Exon 2 of 14	ENSP00000595421.1
EXOC3L1	ENST00000855140.1		c.-196C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 13	ENSP00000525199.1

Frequencies

GnomAD3 genomes

AF:

0.0165

AC:

2516

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0577

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00556

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.0110

GnomAD4 exome

AF:

0.00226

AC:

1037

AN:

458676

Hom.:

Cov.:

AF XY:

0.00187

AC XY:

454

AN XY:

242242

show subpopulations

African (AFR)

AF:

0.0623

AC:

798

AN:

12800

American (AMR)

AF:

0.00253

AC:

AN:

20966

Ashkenazi Jewish (ASJ)

AF:

0.000359

AC:

AN:

13914

East Asian (EAS)

AF:

0.0000645

AC:

AN:

30986

South Asian (SAS)

AF:

0.000128

AC:

AN:

46964

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29182

Middle Eastern (MID)

AF:

0.00253

AC:

AN:

1980

European-Non Finnish (NFE)

AF:

0.000178

AC:

AN:

275572

Other (OTH)

AF:

0.00452

AC:

119

AN:

26312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

147

196

245

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.0166

AC:

2524

AN:

152328

Hom.:

Cov.:

AF XY:

0.0161

AC XY:

1199

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.0577

AC:

2400

AN:

41570

American (AMR)

AF:

0.00556

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

68026

Other (OTH)

AF:

0.0104

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

124

248

373

497

621

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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:

0.00732

Hom.:

Bravo

AF:

0.0195

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.7

(source)

DANN

Benign

0.62

PhyloP100

-0.13

PromoterAI

-0.0088

Neutral

(source)

Mutation Taster

=100/0

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over