chr11-63508945-G-A

Position:

• chr11-63508945-G-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_033101.4(LGALS12):​c.326G>A​(p.Gly109Asp) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LGALS12 NM_033101.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.59

Genes affected

LGALS12 (HGNC:15788): (galectin 12) This gene encodes a member of the galectin superfamily, a group of beta-galactoside-binding proteins with conserved carbohydrate recognition domains. The related mouse protein is a primary regulator of the early stages of adipose tissue development. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, May 2010]

LGALS12 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.967

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGALS12	NM_033101.4	c.326G>A	p.Gly109Asp	missense_variant	3/9	ENST00000394618.9	NP_149092.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGALS12	ENST00000394618.9	c.326G>A	p.Gly109Asp	missense_variant	3/9	1	NM_033101.4	ENSP00000378116.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 09, 2024

The c.395G>A (p.G132D) alteration is located in exon 3 (coding exon 3) of the LGALS12 gene. This alteration results from a G to A substitution at nucleotide position 395, causing the glycine (G) at amino acid position 132 to be replaced by an aspartic acid (D). 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	Benign	0.28
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	.;T;.;.;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.81	T;T;T;T;T
M_CAP	Benign	0.0090	T
MetaRNN	Pathogenic	0.97	D;D;D;D;D
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.7	M;M;.;.;.
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-4.5	D;D;D;D;D
REVEL	Uncertain	0.34
Sift	Benign	0.030	D;T;D;T;T
Sift4G	Uncertain	0.037	D;D;D;D;D
Polyphen		0.98	D;D;.;.;.
Vest4		0.60
MutPred		0.89		Loss of MoRF binding (P = 0.0357);Loss of MoRF binding (P = 0.0357);.;.;.;
MVP		0.54
MPC		0.65
ClinPred		0.90	D
GERP RS		4.5
Varity_R		0.36
gMVP		0.73

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: chr11-63276417;