10-70301425-C-G

Variant names:

• chr10-70301425-C-G
• rs755293571
• NM_001278212.2:c.484G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001278212.2(LRRC20):​c.484G>C​(p.Val162Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. V162M) 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: 2.71
• Publications: 4 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1680986).

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.484G>C	p.Val162Leu	missense	Exon 5 of 5	NP_001265141.1	Q8TCA0-1
	LRRC20	NM_001278211.2		c.484G>C	p.Val162Leu	missense	Exon 5 of 5	NP_001265140.1	Q8TCA0-1
	LRRC20	NM_207119.3		c.484G>C	p.Val162Leu	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.484G>C	p.Val162Leu	missense	Exon 5 of 5	ENSP00000413745.2	Q8TCA0-1
	LRRC20	ENST00000355790.8	TSL:1	c.484G>C	p.Val162Leu	missense	Exon 5 of 5	ENSP00000348043.4	Q8TCA0-1
	LRRC20	ENST00000373224.5	TSL:2	c.484G>C	p.Val162Leu	missense	Exon 5 of 5	ENSP00000362321.1	Q8TCA0-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 249962 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461366 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727016

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52912

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-0.0061
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		2.7
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.045
Sift	Benign	0.36	T
Sift4G	Benign	0.23	T
Polyphen		0.26	B
Vest4		0.10
MutPred		0.28		Gain of catalytic residue at V162 (P = 0.0981)
MVP		0.29
MPC		0.26
ClinPred		0.47	T
GERP RS		5.5
Varity_R		0.078
gMVP		0.66
Mutation Taster		=85/15	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: rs755293571; hg19: chr10-72061181;