10-70323872-C-T

Variant names:

• chr10-70323872-C-T
• rs757588678
• NM_001278212.2:c.391G>A

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.391G>A​(p.Glu131Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,614,028 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E131G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: LRRC20 NM_001278212.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.42
• Publications: 0 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=0.08246714).

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.391G>A	p.Glu131Lys	missense	Exon 4 of 5	NP_001265141.1	Q8TCA0-1
	LRRC20	NM_001278211.2		c.391G>A	p.Glu131Lys	missense	Exon 4 of 5	NP_001265140.1	Q8TCA0-1
	LRRC20	NM_207119.3		c.391G>A	p.Glu131Lys	missense	Exon 4 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.391G>A	p.Glu131Lys	missense	Exon 4 of 5	ENSP00000413745.2	Q8TCA0-1
	LRRC20	ENST00000355790.8	TSL:1	c.391G>A	p.Glu131Lys	missense	Exon 4 of 5	ENSP00000348043.4	Q8TCA0-1
	LRRC20	ENST00000373224.5	TSL:2	c.391G>A	p.Glu131Lys	missense	Exon 4 of 5	ENSP00000362321.1	Q8TCA0-1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152242 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 251022 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000212 AC: 31 AN: 1461786 Hom.: 0 Cov.: 32 AF XY: 0.0000289 AC XY: 21 AN XY: 727204

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

American (AMR) AF: 0.0000447 AC: 2 AN: 44722

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

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000252 AC: 28 AN: 1111988

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152242 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74378

African (AFR) AF: 0.0000241 AC: 1 AN: 41472

American (AMR) AF: 0.000131 AC: 2 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.0042	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.14	N
PhyloP100		1.4
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.038
Sift	Benign	0.34	T
Sift4G	Uncertain	0.044	D
Polyphen		0.0	B
Vest4		0.46
MVP		0.54
MPC		0.55
ClinPred		0.27	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.052
gMVP		0.35
Mutation Taster		=82/18	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: rs757588678; hg19: chr10-72083628; COSMIC: COSV62937077;