12-58877657-C-A

Position:

• chr12-58877657-C-A

Variant summary

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

The NM_153377.5(LRIG3):​c.2279G>T​(p.Ser760Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LRIG3 NM_153377.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.79

Genes affected

LRIG3 (HGNC:30991): (leucine rich repeats and immunoglobulin like domains 3) Predicted to act upstream of or within otolith morphogenesis. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRIG3	NM_153377.5	c.2279G>T	p.Ser760Ile	missense_variant	15/19	ENST00000320743.8	NP_700356.2
LRIG3	NM_001136051.3	c.2099G>T	p.Ser700Ile	missense_variant	15/19		NP_001129523.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRIG3	ENST00000320743.8	c.2279G>T	p.Ser760Ile	missense_variant	15/19	1	NM_153377.5	ENSP00000326759	P1
LRIG3	ENST00000379141.8	c.2099G>T	p.Ser700Ile	missense_variant	15/19	1		ENSP00000368436
LRIG3	ENST00000433272.6	c.*517G>T		3_prime_UTR_variant, NMD_transcript_variant	16/20	1		ENSP00000413143

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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 11, 2022

The c.2279G>T (p.S760I) alteration is located in exon 15 (coding exon 15) of the LRIG3 gene. This alteration results from a G to T substitution at nucleotide position 2279, causing the serine (S) at amino acid position 760 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	Uncertain	0.39
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	.;T
Eigen	Benign	0.095
Eigen_PC	Benign	0.059
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.58	D;D
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.9	.;L
MutationTaster	Benign	0.99	N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Benign	0.15
Sift	Benign	0.056	T;T
Sift4G	Uncertain	0.012	D;D
Polyphen		0.67	P;P
Vest4		0.42
MutPred		0.44		.;Loss of disorder (P = 0.0379);
MVP		0.48
MPC		0.25
ClinPred		0.85	D
GERP RS		3.4
Varity_R		0.11
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr12-59271439;