chr6-63280368-T-C

Position:

• chr6-63280368-T-C

Variant summary

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

The NM_016571.3(LGSN):​c.1183A>G​(p.Ile395Val) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LGSN NM_016571.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.476

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=0.17082012).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LGSN	NM_016571.3	c.1183A>G	p.Ile395Val	missense_variant	4/4	ENST00000370657.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LGSN	ENST00000370657.9	c.1183A>G	p.Ile395Val	missense_variant	4/4	1	NM_016571.3	P1
LGSN	ENST00000370658.9	c.*135A>G		3_prime_UTR_variant	5/5	1
LGSN	ENST00000622415.1	c.*908A>G		3_prime_UTR_variant	5/5	2
LGSN	ENST00000485906.6	c.529+654A>G		intron_variant		3

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 13, 2023

The c.1183A>G (p.I395V) alteration is located in exon 4 (coding exon 4) of the LGSN gene. This alteration results from a A to G substitution at nucleotide position 1183, causing the isoleucine (I) at amino acid position 395 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	0.072
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	3.5
DANN	Benign	0.26
DEOGEN2	Benign	0.032	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.015	N
MutationTaster	Benign	0.70	D;D
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.16	N
REVEL	Benign	0.20
Sift	Benign	0.99	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.090
MutPred		0.74		Loss of stability (P = 0.1541);
MVP		0.57
MPC		0.013
ClinPred		0.042	T
GERP RS		2.2
Varity_R		0.039
gMVP		0.34

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: chr6-63990273;