rs749513430

Variant names:

• chr12-10218096-C-T
• rs749513430
• NM_031412.4:c.124C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_031412.4(GABARAPL1):​c.124C>T​(p.Pro42Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GABARAPL1 NM_031412.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.23
• Publications: 2 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31250966).

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.124C>T	p.Pro42Ser	missense	Exon 2 of 4	NP_113600.1	Q9H0R8-1
	GABARAPL1	NM_001363598.2		c.124C>T	p.Pro42Ser	missense	Exon 2 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.124C>T	p.Pro42Ser	missense	Exon 2 of 4	ENSP00000266458.5	Q9H0R8-1
	GABARAPL1	ENST00000421801.6	TSL:2	c.124C>T	p.Pro42Ser	missense	Exon 2 of 3	ENSP00000411256.2	Q9H0R8-2
	GABARAPL1	ENST00000543602.5	TSL:5	c.124C>T	p.Pro42Ser	missense	Exon 3 of 4	ENSP00000445857.1	Q9H0R8-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251484 AF XY: 0.00000736

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458482 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 725874

African (AFR) AF: 0.0000299 AC: 1 AN: 33406

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108904

Other (OTH) AF: 0.00 AC: 0 AN: 60296

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

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	Benign	0.16
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.86	T
PhyloP100		6.2
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.095
Sift	Benign	0.086	T
Sift4G	Benign	0.13	T
Polyphen		0.0030	B
Vest4		0.38
MutPred		0.65		Gain of phosphorylation at P42 (P = 0.0127)
MVP		0.46
MPC		0.46
ClinPred		0.48	T
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.45
gMVP		0.80
Mutation Taster		=57/43	polymorphism

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

dbSNP: rs749513430; hg19: chr12-10370695; COSMIC: COSV56770813; COSMIC: COSV56770813;