10-70323898-A-G

Position:

• chr10-70323898-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001278212.2(LRRC20):​c.365T>C​(p.Leu122Pro) 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. Variant has been reported in ClinVar 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: 7.24

Genes affected

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

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.943

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC20	NM_001278212.2	c.365T>C	p.Leu122Pro	missense_variant	4/5	ENST00000446961.4	NP_001265141.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC20	ENST00000446961.4	c.365T>C	p.Leu122Pro	missense_variant	4/5	2	NM_001278212.2	ENSP00000413745.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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

Feb 15, 2023

The c.365T>C (p.L122P) alteration is located in exon 4 (coding exon 3) of the LRRC20 gene. This alteration results from a T to C substitution at nucleotide position 365, causing the leucine (L) at amino acid position 122 to be replaced by a proline (P). 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	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Pathogenic	0.40
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.46	.;T;T;T;.;.
Eigen	Pathogenic	0.94
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.83	T;T;.;D;.;T
M_CAP	Pathogenic	0.33	D
MetaRNN	Pathogenic	0.94	D;D;D;D;D;D
MetaSVM	Pathogenic	0.86	D
MutationAssessor	Pathogenic	4.1	.;.;H;H;.;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-6.8	D;.;D;D;D;D
REVEL	Pathogenic	0.90
Sift	Pathogenic	0.0	D;.;D;D;D;D
Sift4G	Uncertain	0.0030	D;D;D;D;D;.
Polyphen		1.0	D;.;D;D;D;.
Vest4		0.97
MutPred		0.76		.;.;Loss of stability (P = 0.0085);Loss of stability (P = 0.0085);.;Loss of stability (P = 0.0085);
MVP		0.99
MPC		0.93
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.94
gMVP		0.96

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-72083654;