NM_001278212.2:c.392A>G

Variant names:

• chr10-70323871-T-C
• NM_001278212.2:c.392A>G

Variant summary

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

The NM_001278212.2(LRRC20):​c.392A>G​(p.Glu131Gly) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E131K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LRRC20 NM_001278212.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.40
• Publications: 0 publications found

Genes affected

LRRC20 (HGNC:23421): (leucine rich repeat containing 20)

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=0.2766102).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278212.2. 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
	LRRC20	NM_001278212.2	MANE Select	c.392A>G	p.Glu131Gly	missense	Exon 4 of 5	NP_001265141.1	Q8TCA0-1
	LRRC20	NM_001278211.2		c.392A>G	p.Glu131Gly	missense	Exon 4 of 5	NP_001265140.1	Q8TCA0-1
	LRRC20	NM_207119.3		c.392A>G	p.Glu131Gly	missense	Exon 4 of 5	NP_997002.1	Q8TCA0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC20	ENST00000446961.4	TSL:2 MANE Select	c.392A>G	p.Glu131Gly	missense	Exon 4 of 5	ENSP00000413745.2	Q8TCA0-1
	LRRC20	ENST00000355790.8	TSL:1	c.392A>G	p.Glu131Gly	missense	Exon 4 of 5	ENSP00000348043.4	Q8TCA0-1
	LRRC20	ENST00000373224.5	TSL:2	c.392A>G	p.Glu131Gly	missense	Exon 4 of 5	ENSP00000362321.1	Q8TCA0-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.057	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.098
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N
PhyloP100		3.4
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.11
Sift	Benign	0.066	T
Sift4G	Uncertain	0.022	D
Polyphen		0.0040	B
Vest4		0.58
MutPred		0.46		Loss of stability (P = 0.0077)
MVP		0.71
MPC		0.63
ClinPred		0.92	D
GERP RS		3.9
Varity_R		0.11
gMVP		0.42
Mutation Taster		=80/20	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

hg19: chr10-72083627;