12-58874229-A-T

Position:

• chr12-58874229-A-T

Variant summary

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

The NM_153377.5(LRIG3):​c.2941T>A​(p.Cys981Ser) 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: 33)
• Consequence: LRIG3 NM_153377.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.46

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09812197).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRIG3	NM_153377.5	c.2941T>A	p.Cys981Ser	missense_variant	18/19	ENST00000320743.8	NP_700356.2
LRIG3	NM_001136051.3	c.2761T>A	p.Cys921Ser	missense_variant	18/19		NP_001129523.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRIG3	ENST00000320743.8	c.2941T>A	p.Cys981Ser	missense_variant	18/19	1	NM_153377.5	ENSP00000326759	P1

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

Dec 22, 2023

The c.2941T>A (p.C981S) alteration is located in exon 18 (coding exon 18) of the LRIG3 gene. This alteration results from a T to A substitution at nucleotide position 2941, causing the cysteine (C) at amino acid position 981 to be replaced by a serine (S). 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	0.24
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	11
DANN	Benign	0.43
DEOGEN2	Benign	0.074	.;T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.55	T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.098	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	.;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.29	N;N
REVEL	Benign	0.070
Sift	Benign	0.15	T;T
Sift4G	Benign	0.43	T;T
Polyphen		0.0	B;B
Vest4		0.24
MutPred		0.33		.;Gain of phosphorylation at C981 (P = 0.0042);
MVP		0.56
MPC		0.22
ClinPred		0.077	T
GERP RS		1.9
Varity_R		0.048
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr12-59268011;