12-10213161-T-C

Variant names:

• chr12-10213161-T-C
• NM_031412.4:c.32T>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_031412.4(GABARAPL1):​c.32T>C​(p.Phe11Ser) 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)
• Consequence: GABARAPL1 NM_031412.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.87

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.807

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABARAPL1	NM_031412.4	c.32T>C	p.Phe11Ser	missense_variant	Exon 1 of 4	ENST00000266458.10	NP_113600.1
GABARAPL1	NM_001363598.2	c.32T>C	p.Phe11Ser	missense_variant	Exon 1 of 3		NP_001350527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABARAPL1	ENST00000266458.10	c.32T>C	p.Phe11Ser	missense_variant	Exon 1 of 4	1	NM_031412.4	ENSP00000266458.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.32T>C (p.F11S) alteration is located in exon 1 (coding exon 1) of the GABARAPL1 gene. This alteration results from a T to C substitution at nucleotide position 32, causing the phenylalanine (F) at amino acid position 11 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;T;.;.;T;.;T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.69	T;.;.;.;T;T;T
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.81	D;D;D;D;D;D;D
MetaSVM	Benign	-0.31	T
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-5.9	D;D;D;D;.;D;D
REVEL	Uncertain	0.52
Sift	Pathogenic	0.0	D;D;D;D;.;D;D
Sift4G	Uncertain	0.032	D;D;D;D;D;D;D
Polyphen		0.90	.;P;.;.;.;.;P
Vest4		0.75, 0.74, 0.74, 0.78, 0.78, 0.77
MutPred		0.43		Gain of phosphorylation at F11 (P = 0.0054);Gain of phosphorylation at F11 (P = 0.0054);Gain of phosphorylation at F11 (P = 0.0054);Gain of phosphorylation at F11 (P = 0.0054);Gain of phosphorylation at F11 (P = 0.0054);Gain of phosphorylation at F11 (P = 0.0054);Gain of phosphorylation at F11 (P = 0.0054);
MVP		0.82
MPC		0.89
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.89
gMVP		0.93

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-10365760;