Genetic Variant GABARAPL3:n.1164A>T (chr15-90348750-A-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NR_028287.1(GABARAPL3):n.698T>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. 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 0.0062 ( 0 hom., cov: 25)

Exomes 𝑓: 0.039 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GABARAPL3
NR_028287.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.53

Publications

8 publications found

Variant links:

Genes affected

GABARAPL3 (HGNC:):

GABARAPL3 links:

GABARAPL3 (HGNC:4069): (GABA type A receptor associated protein like 3 (pseudogene)) Predicted to enable GABA receptor binding activity and ubiquitin protein ligase binding activity. Predicted to be involved in autophagosome assembly; autophagy of mitochondrion; and cellular response to nitrogen starvation. Predicted to be located in cytoplasmic vesicle and microtubule. Predicted to be active in autophagosome membrane and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

GABARAPL3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_028287.1. 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
	GABARAPL3	NR_028287.1		n.698T>A		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
GABARAPL3	ENST00000624044.1	TSL:6	n.1164A>T	non_coding_transcript_exon	Exon 1 of 1
ENSG00000310490	ENST00000850385.1		n.126+134T>A	intron	N/A
GABARAPL3	ENST00000412799.3	TSL:6	n.*94T>A	downstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.00626

AC:

637

AN:

101830

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0101

Gnomad AMI

AF:

0.00314

Gnomad AMR

AF:

0.00483

Gnomad ASJ

AF:

0.0109

Gnomad EAS

AF:

0.00862

Gnomad SAS

AF:

0.00762

Gnomad FIN

AF:

0.00267

Gnomad MID

AF:

0.00485

Gnomad NFE

AF:

0.00487

Gnomad OTH

AF:

0.00441

GnomAD4 exome

AF:

0.0392

AC:

17371

AN:

442636

Hom.:

Cov.:

AF XY:

0.0364

AC XY:

8711

AN XY:

239382

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0409

AC:

469

AN:

11460

American (AMR)

AF:

0.0591

AC:

1243

AN:

21040

Ashkenazi Jewish (ASJ)

AF:

0.0296

AC:

424

AN:

14342

East Asian (EAS)

AF:

0.0222

AC:

689

AN:

31046

South Asian (SAS)

AF:

0.0479

AC:

2131

AN:

44474

European-Finnish (FIN)

AF:

0.0175

AC:

594

AN:

33870

Middle Eastern (MID)

AF:

0.0168

AC:

AN:

2976

European-Non Finnish (NFE)

AF:

0.0421

AC:

10891

AN:

258676

Other (OTH)

AF:

0.0356

AC:

880

AN:

24752

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.292

Heterozygous variant carriers

1213

2426

3640

4853

6066

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

132

264

396

528

660

<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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00624

AC:

636

AN:

101932

Hom.:

Cov.:

AF XY:

0.00610

AC XY:

308

AN XY:

50474

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0101

AC:

237

AN:

23512

American (AMR)

AF:

0.00483

AC:

AN:

10356

Ashkenazi Jewish (ASJ)

AF:

0.0109

AC:

AN:

2392

East Asian (EAS)

AF:

0.00864

AC:

AN:

3702

South Asian (SAS)

AF:

0.00735

AC:

AN:

3536

European-Finnish (FIN)

AF:

0.00267

AC:

AN:

8232

Middle Eastern (MID)

AF:

0.00526

AC:

AN:

190

European-Non Finnish (NFE)

AF:

0.00488

AC:

234

AN:

47996

Other (OTH)

AF:

0.00435

AC:

AN:

1380

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.251

Heterozygous variant carriers

180

270

360

450

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:

0.000133

Hom.:

3185

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.50

(source)

DANN

Benign

0.81

PhyloP100

-1.5

Splicing

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