chr10-70301362-G-C

Variant names:

• chr10-70301362-G-C
• rs149973737
• NM_001278212.2:c.547C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001278212.2(LRRC20):​c.547C>G​(p.Leu183Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. L183I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LRRC20 NM_001278212.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06286973).

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.547C>G	p.Leu183Val	missense	Exon 5 of 5	NP_001265141.1	Q8TCA0-1
	LRRC20	NM_001278211.2		c.547C>G	p.Leu183Val	missense	Exon 5 of 5	NP_001265140.1	Q8TCA0-1
	LRRC20	NM_207119.3		c.547C>G	p.Leu183Val	missense	Exon 5 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.547C>G	p.Leu183Val	missense	Exon 5 of 5	ENSP00000413745.2	Q8TCA0-1
	LRRC20	ENST00000355790.8	TSL:1	c.547C>G	p.Leu183Val	missense	Exon 5 of 5	ENSP00000348043.4	Q8TCA0-1
	LRRC20	ENST00000373224.5	TSL:2	c.547C>G	p.Leu183Val	missense	Exon 5 of 5	ENSP00000362321.1	Q8TCA0-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460084 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 726362

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44600

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111652

Other (OTH) AF: 0.00 AC: 0 AN: 60344

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	10
DANN	Benign	0.59
DEOGEN2	Benign	0.0090	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.1
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.022
Sift	Benign	0.31	T
Sift4G	Benign	0.36	T
Polyphen		0.0040	B
Vest4		0.062
MutPred		0.38		Loss of glycosylation at P184 (P = 0.081)
MVP		0.22
MPC		0.36
ClinPred		0.072	T
GERP RS		3.6
Varity_R		0.038
gMVP		0.39
Mutation Taster		=98/2	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: rs149973737; hg19: chr10-72061118;