4-109869900-C-A

Variant names:

• chr4-109869900-C-A
• NM_198506.5:c.1151C>A
• LRIT3 p.Ser384*

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_198506.5(LRIT3):​c.1151C>A​(p.Ser384*) variant causes a stop gained 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S384S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRIT3 NM_198506.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.418
• Publications: 0 publications found

Genes affected

LRIT3 (HGNC:24783): (leucine rich repeat, Ig-like and transmembrane domains 3) This gene encodes a protein that has a fibronectin type III domain and a C-terminal transmembrane domain, as well as a leucine-rich repeat domain and immunoglobulin-like domain near the N-terminus. The encoded protein may regulate fibroblast growth factor receptors and affect the modification of these receptors, which are glycosylated differently in the Golgi and endoplasmic reticulum. Mutations in this gene are associated with congenital stationary night blindness, type 1F. [provided by RefSeq, May 2013]

LRIT3 Gene-Disease associations (from GenCC):

• congenital stationary night blindness 1F

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• congenital stationary night blindness

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000296171 (HGNC:):

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.436 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198506.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRIT3	NM_198506.5	MANE Select	c.1151C>A	p.Ser384*	stop_gained	Exon 4 of 4	NP_940908.3	Q3SXY7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRIT3	ENST00000594814.6	TSL:5 MANE Select	c.1151C>A	p.Ser384*	stop_gained	Exon 4 of 4	ENSP00000469759.1	Q3SXY7-1
	LRIT3	ENST00000876618.1		c.1151C>A	p.Ser384*	stop_gained	Exon 5 of 5	ENSP00000546677.1
	LRIT3	ENST00000327908.3	TSL:2	c.602C>A	p.Ser201*	stop_gained	Exon 4 of 4	ENSP00000328222.3	A0A0A0MR64

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	33
DANN	Uncertain	0.99
Eigen	Benign	0.010
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.22	N
PhyloP100		0.42
Mutation Taster		=5/195	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr4-110791056;