chr6-63280098-C-T

Position:

• chr6-63280098-C-T

Variant summary

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

The NM_016571.3(LGSN):​c.1453G>A​(p.Val485Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign 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: LGSN NM_016571.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.67

Genes affected

LGSN (HGNC:21016): (lengsin, lens protein with glutamine synthetase domain) This gene encodes a protein with similarity to the GS I members of the glutamine synthetase superfamily. The encoded protein is referred to as a pseudo-glutamine synthetase because it has no glutamine synthesis activity and may function as a chaperone protein. This protein is localized to the lens and may be associated with cataract disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2009]

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=0.13640478).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGSN	NM_016571.3	c.1453G>A	p.Val485Ile	missense_variant	4/4	ENST00000370657.9	NP_057655.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGSN	ENST00000370657.9	c.1453G>A	p.Val485Ile	missense_variant	4/4	1	NM_016571.3	ENSP00000359691.4
LGSN	ENST00000370658	c.*405G>A		3_prime_UTR_variant	5/5	1		ENSP00000359692.5
LGSN	ENST00000622415.1	c.*1178G>A		3_prime_UTR_variant	5/5	2		ENSP00000479173.1
LGSN	ENST00000485906.6	c.530-671G>A		intron_variant		3		ENSP00000431246.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Aug 01, 2024

The c.1453G>A (p.V485I) alteration is located in exon 4 (coding exon 4) of the LGSN gene. This alteration results from a G to A substitution at nucleotide position 1453, causing the valine (V) at amino acid position 485 to be replaced by an isoleucine (I). 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	0.077
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Benign	0.64
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.17
Eigen_PC	Benign	0.076
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.0	L
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.040	N
REVEL	Uncertain	0.33
Sift	Benign	0.46	T
Sift4G	Benign	0.98	T
Polyphen		0.025	B
Vest4		0.10
MutPred		0.41		Gain of ubiquitination at K488 (P = 0.1375);
MVP		0.63
MPC		0.013
ClinPred		0.81	D
GERP RS		5.1
Varity_R		0.10
gMVP		0.11

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: chr6-63990003;