12-10213215-T-A

Variant names:

• chr12-10213215-T-A
• NM_031412.4:c.86T>A
• GABARAPL1 p.Val29Asp

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_031412.4(GABARAPL1):​c.86T>A​(p.Val29Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GABARAPL1 NM_031412.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.81
• Publications: 0 publications found

Genes affected

GABARAPL1 (HGNC:4068): (GABA type A receptor associated protein like 1) Enables Tat protein binding activity and ubiquitin protein ligase binding activity. Predicted to be involved in autophagosome assembly; autophagy of mitochondrion; and cellular response to nitrogen starvation. Located in autophagosome. Colocalizes with mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000309675 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.915

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031412.4. 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
	GABARAPL1	NM_031412.4	MANE Select	c.86T>A	p.Val29Asp	missense	Exon 1 of 4	NP_113600.1	Q9H0R8-1
	GABARAPL1	NM_001363598.2		c.86T>A	p.Val29Asp	missense	Exon 1 of 3	NP_001350527.1	Q9H0R8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABARAPL1	ENST00000266458.10	TSL:1 MANE Select	c.86T>A	p.Val29Asp	missense	Exon 1 of 4	ENSP00000266458.5	Q9H0R8-1
	GABARAPL1	ENST00000421801.6	TSL:2	c.86T>A	p.Val29Asp	missense	Exon 1 of 3	ENSP00000411256.2	Q9H0R8-2
	GABARAPL1	ENST00000543602.5	TSL:5	c.86T>A	p.Val29Asp	missense	Exon 2 of 4	ENSP00000445857.1	Q9H0R8-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1307528 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 650218

African (AFR) AF: 0.00 AC: 0 AN: 30346

American (AMR) AF: 0.00 AC: 0 AN: 35452

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23232

East Asian (EAS) AF: 0.00 AC: 0 AN: 34902

South Asian (SAS) AF: 0.00 AC: 0 AN: 79044

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5354

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1002270

Other (OTH) AF: 0.00 AC: 0 AN: 53576

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	28
DANN	Benign	0.97
DEOGEN2	Benign	0.30	T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Uncertain	-0.028	T
PhyloP100		4.8
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-6.6	D
REVEL	Pathogenic	0.66
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
PromoterAI		0.064	Neutral
Varity_R		0.98
gMVP		0.96
Mutation Taster		=42/58	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-10365814;