11-40115514-C-A

Variant names:

• chr11-40115514-C-A
• rs760514279
• NM_001258419.2:c.779G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001258419.2(LRRC4C):​c.779G>T​(p.Arg260Leu) variant causes a missense change involving the alteration of a 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R260Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRRC4C NM_001258419.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91
• Publications: 0 publications found

Genes affected

LRRC4C (HGNC:29317): (leucine rich repeat containing 4C) NGL1 is a specific binding partner for netrin G1 (NTNG1; MIM 608818), which is a member of the netrin family of axon guidance molecules (Lin et al., 2003 [PubMed 14595443]).[supplied by OMIM, Mar 2008]

ENSG00000306946 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.821

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001258419.2. 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
	LRRC4C	NM_001258419.2	MANE Select	c.779G>T	p.Arg260Leu	missense	Exon 7 of 7	NP_001245348.1	Q9HCJ2
	LRRC4C	NM_020929.3		c.779G>T	p.Arg260Leu	missense	Exon 5 of 5	NP_065980.1	Q9HCJ2
	LRRC4C	NR_047673.1		n.1812G>T		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC4C	ENST00000528697.6	TSL:1 MANE Select	c.779G>T	p.Arg260Leu	missense	Exon 7 of 7	ENSP00000437132.1	Q9HCJ2
	LRRC4C	ENST00000278198.2	TSL:1	c.779G>T	p.Arg260Leu	missense	Exon 2 of 2	ENSP00000278198.1	Q9HCJ2
	LRRC4C	ENST00000527150.5	TSL:1	c.779G>T	p.Arg260Leu	missense	Exon 3 of 3	ENSP00000436976.1	Q9HCJ2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Benign	0.052	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.51	N
PhyloP100		7.9
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.059	T
Polyphen		0.99	D
Vest4		0.86
MutPred		0.59		Gain of catalytic residue at R260 (P = 0.0546)
MVP		0.43
MPC		1.7
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.66
gMVP		0.55
Mutation Taster		=41/59	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

Other links and lift over

dbSNP: rs760514279; hg19: chr11-40137064; COSMIC: COSV99537469; COSMIC: COSV99537469;