NM_007285.7:c.19G>A

Variant names:

• chr16-75566505-G-A
• NM_007285.7:c.19G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_007285.7(GABARAPL2):​c.19G>A​(p.Glu7Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GABARAPL2 NM_007285.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.85
• Publications: 0 publications found

Genes affected

GABARAPL2 (HGNC:13291): (GABA type A receptor associated protein like 2) Enables ubiquitin protein ligase binding activity. Involved in negative regulation of proteasomal protein catabolic process and protein localization to endoplasmic reticulum. Located in Golgi membrane and autophagosome membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000259992 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007285.7. 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
	GABARAPL2	NM_007285.7	MANE Select	c.19G>A	p.Glu7Lys	missense	Exon 1 of 4	NP_009216.1	P60520

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABARAPL2	ENST00000037243.7	TSL:1 MANE Select	c.19G>A	p.Glu7Lys	missense	Exon 1 of 4	ENSP00000037243.2	P60520
	GABARAPL2	ENST00000563744.1	TSL:1	c.19G>A	p.Glu7Lys	missense	Exon 1 of 3	ENSP00000457448.1	H3BU36
	GABARAPL2	ENST00000565057.5	TSL:2	c.19G>A	p.Glu7Lys	missense	Exon 1 of 3	ENSP00000456773.1	H3BSM5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	Uncertain	0.37
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.052
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		8.8
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.21
Sift	Benign	0.18	T
Sift4G	Benign	0.24	T
Polyphen		0.0020	B
Vest4		0.73
MutPred		0.40		Gain of MoRF binding (P = 7e-04)
MVP		0.52
MPC		0.99
ClinPred		0.97	D
GERP RS		4.0
PromoterAI		0.0088	Neutral
Varity_R		0.76
gMVP		0.58

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

Other links and lift over

hg19: chr16-75600403;