rs755293571

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr10-70301425-C-G
• chr10-70301425-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/21 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

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC20	NM_001278212.2	c.484G>C	p.Val162Leu	missense_variant	Exon 5 of 5	ENST00000446961.4	NP_001265141.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC20	ENST00000446961.4	c.484G>C	p.Val162Leu	missense_variant	Exon 5 of 5	2	NM_001278212.2	ENSP00000413745.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 249962 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135270

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 SAS 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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;T;.;.;.
Eigen	Benign	-0.0061
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.80	T;T;.;T;.;T;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.17	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	.;.;L;L;.;.;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.16	N;.;N;N;N;N;N
REVEL	Benign	0.045
Sift	Benign	0.36	T;.;T;T;T;T;T
Sift4G	Benign	0.23	T;T;T;T;T;T;.
Polyphen		0.26	B;.;B;B;B;B;.
Vest4		0.10
MutPred		0.28		.;.;Gain of catalytic residue at V162 (P = 0.0981);Gain of catalytic residue at V162 (P = 0.0981);.;.;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

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: rs755293571; hg19: chr10-72061181;