rs9352774

Positions:

• chr6-63304907-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016571.3(LGSN):​c.31-9862T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,172 control chromosomes in the GnomAD database, including 1,220 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (1220 hom., cov: 32)
• Consequence: LGSN NM_016571.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.313

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGSN	NM_016571.3	c.31-9862T>G		intron_variant		ENST00000370657.9	NP_057655.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGSN	ENST00000370657.9	c.31-9862T>G		intron_variant		1	NM_016571.3	ENSP00000359691.4
LGSN	ENST00000370658.9	c.31-9862T>G		intron_variant		1		ENSP00000359692.5
LGSN	ENST00000485906.6	c.31-9862T>G		intron_variant		3		ENSP00000431246.2
LGSN	ENST00000622415.1	c.31-9862T>G		intron_variant		2		ENSP00000479173.1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15659 AN: 152054 Hom.: 1210 Cov.: 32

Gnomad AFR AF: 0.0254

Gnomad AMI AF: 0.0967

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.0671

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.0890

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.103 AC: 15684 AN: 152172 Hom.: 1220 Cov.: 32 AF XY: 0.106 AC XY: 7908 AN XY: 74382

Gnomad4 AFR AF: 0.0253

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.0671

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.0900

Alfa AF: 0.114 Hom.: 1239

Bravo AF: 0.110

Asia WGS AF: 0.136 AC: 472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.88

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

LitVar

Other links and lift over

dbSNP: rs9352774; hg19: chr6-64014812;