10-70340648-C-T

Position:

• chr10-70340648-C-T

Variant summary

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

The NM_001278212.2(LRRC20):​c.137G>A​(p.Arg46Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: LRRC20 NM_001278212.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.07

Genes affected

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

LRRC20 (HGNC:):

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
LRRC20	NM_001278212.2	c.137G>A	p.Arg46Gln	missense_variant	3/5	ENST00000446961.4	NP_001265141.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC20	ENST00000446961.4	c.137G>A	p.Arg46Gln	missense_variant	3/5	2	NM_001278212.2	ENSP00000413745.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461882 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727242

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000629

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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

Jun 25, 2024

The c.137G>A (p.R46Q) alteration is located in exon 3 (coding exon 2) of the LRRC20 gene. This alteration results from a G to A substitution at nucleotide position 137, causing the arginine (R) at amino acid position 46 to be replaced by a glutamine (Q). 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	0.12
BayesDel_addAF	Benign	-0.0084	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.22	T;T;.;.
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.78	.;T;T;T
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.47	T;T;T;T
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.3	M;M;M;.
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.2	D;D;D;D
REVEL	Benign	0.10
Sift	Benign	0.033	D;D;T;D
Sift4G	Benign	0.23	T;T;D;.
Polyphen		1.0	D;D;P;.
Vest4		0.75
MutPred		0.46		Loss of MoRF binding (P = 0.0651);Loss of MoRF binding (P = 0.0651);Loss of MoRF binding (P = 0.0651);Loss of MoRF binding (P = 0.0651);
MVP		0.80
MPC		0.33
ClinPred		0.97	D
GERP RS		5.7
Varity_R		0.29
gMVP		0.39

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

Publications

LitVar

Other links and lift over

dbSNP: rs1564629152; hg19: chr10-72100404;