11-63509863-T-C

Position:

• chr11-63509863-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_033101.4(LGALS12):​c.458T>C​(p.Ile153Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 32)
• Consequence: LGALS12 NM_033101.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.13

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.896

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGALS12	NM_033101.4	c.458T>C	p.Ile153Thr	missense_variant	4/9	ENST00000394618.9	NP_149092.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGALS12	ENST00000394618.9	c.458T>C	p.Ile153Thr	missense_variant	4/9	1	NM_033101.4	ENSP00000378116.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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 27, 2023

The c.527T>C (p.I176T) alteration is located in exon 4 (coding exon 4) of the LGALS12 gene. This alteration results from a T to C substitution at nucleotide position 527, causing the isoleucine (I) at amino acid position 176 to be replaced by a threonine (T). 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	0.67
BayesDel_addAF	Uncertain	0.084	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.17	.;T;.;.;.
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.82	T;T;T;T;T
M_CAP	Benign	0.0071	T
MetaRNN	Pathogenic	0.90	D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;L;.;.;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.4	D;D;D;D;D
REVEL	Benign	0.23
Sift	Uncertain	0.0010	D;D;D;D;D
Sift4G	Uncertain	0.047	D;D;D;D;D
Polyphen		0.83	P;P;.;.;.
Vest4		0.73
MutPred		0.73		Loss of stability (P = 0.0312);Loss of stability (P = 0.0312);.;.;.;
MVP		0.36
MPC		0.38
ClinPred		0.96	D
GERP RS		5.5
Varity_R		0.68
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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-63277335;