4-109848292-G-C

Variant names:

• chr4-109848292-G-C
• rs747506214
• NM_198506.5:c.91G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_198506.5(LRIT3):​c.91G>C​(p.Gly31Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000185 in 1,079,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G31S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: LRIT3 NM_198506.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.49
• 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]

RRH (HGNC:10450): (retinal pigment epithelium-derived rhodopsin homolog) Opsins are members of the guanine nucleotide-binding protein (G protein)-coupled receptor superfamily. This gene belongs to the seven-exon subfamily of mammalian opsin genes that includes opsin 5 and retinal G protein coupled receptor. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39144307).

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.91G>C	p.Gly31Arg	missense	Exon 1 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.91G>C	p.Gly31Arg	missense	Exon 1 of 4	ENSP00000469759.1	Q3SXY7-1
	LRIT3	ENST00000876618.1		c.91G>C	p.Gly31Arg	missense	Exon 2 of 5	ENSP00000546677.1
	RRH	ENST00000652276.1		c.*4095G>C		3_prime_UTR	Exon 4 of 4	ENSP00000498977.1	A0A494C1B2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000185 AC: 2 AN: 1079626 Hom.: 0 Cov.: 29 AF XY: 0.00000392 AC XY: 2 AN XY: 509662

African (AFR) AF: 0.00 AC: 0 AN: 22962

American (AMR) AF: 0.00 AC: 0 AN: 8418

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14386

East Asian (EAS) AF: 0.0000754 AC: 2 AN: 26520

South Asian (SAS) AF: 0.00 AC: 0 AN: 19490

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2914

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 919742

Other (OTH) AF: 0.00 AC: 0 AN: 43664

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	20
DANN	Benign	0.61
DEOGEN2	Benign	0.0054	T
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.39	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.5
PrimateAI	Benign	0.44	T
Sift4G	Uncertain	0.042	D
Vest4		0.48
MVP		0.62
MPC		0.28
GERP RS		3.8
PromoterAI		-0.00040	Neutral
Varity_R		0.088
gMVP		0.66
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs747506214; hg19: chr4-110769448;