19-39658644-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001190441.3(LGALS16):c.277A>G(p.Ile93Val) 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 benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: LGALS16 NM_001190441.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.36

Genes affected

LGALS16 (HGNC:40039): (galectin 16) Enables lactose binding activity. Involved in positive regulation of T cell apoptotic process. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21960732).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LGALS16	NM_001190441.3	c.277A>G	p.Ile93Val	missense_variant	3/4	ENST00000392051.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LGALS16	ENST00000392051.4	c.277A>G	p.Ile93Val	missense_variant	3/4	1	NM_001190441.3	P1
LGALS16	ENST00000594480.1	c.*149A>G		3_prime_UTR_variant, NMD_transcript_variant	3/4	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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

Apr 22, 2022

The c.277A>G (p.I93V) alteration is located in exon 3 (coding exon 3) of the LGALS16 gene. This alteration results from a A to G substitution at nucleotide position 277, causing the isoleucine (I) at amino acid position 93 to be replaced by a valine (V). 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	0.21
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
Cadd	Benign	1.6
Dann	Uncertain	0.99
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.0011	N
M_CAP	Benign	0.00072	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.12
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.022	D
Vest4		0.36
MutPred		0.58		Loss of catalytic residue at I93 (P = 0.2742);
MVP		0.085
MPC		0.069
ClinPred		0.27	T
GERP RS		-2.4
gMVP		0.29

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: chr19-40149284;