12-69610698-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_201550.4(LRRC10):ā€‹c.141C>Gā€‹(p.His47Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)

Consequence

LRRC10
NM_201550.4 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0230
Variant links:
Genes affected
LRRC10 (HGNC:20264): (leucine rich repeat containing 10) Predicted to enable actin binding activity. Predicted to be involved in cardiac muscle cell development. Predicted to be located in myofibril. Predicted to be active in cytoskeleton and sarcomere. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.07352811).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LRRC10NM_201550.4 linkc.141C>G p.His47Gln missense_variant 1/1 ENST00000361484.5 NP_963844.2 Q5BKY1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LRRC10ENST00000361484.5 linkc.141C>G p.His47Gln missense_variant 1/16 NM_201550.4 ENSP00000355166.3 Q5BKY1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152184
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152184
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.092
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
6.1
DANN
Benign
0.69
DEOGEN2
Benign
0.080
T
Eigen
Benign
-0.86
Eigen_PC
Benign
-0.82
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.56
T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.074
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.81
N
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-0.32
N
REVEL
Benign
0.024
Sift
Benign
0.59
T
Sift4G
Benign
0.33
T
Polyphen
0.010
B
Vest4
0.076
MutPred
0.41
Gain of catalytic residue at L46 (P = 0.0222);
MVP
0.67
MPC
0.20
ClinPred
0.050
T
GERP RS
-0.83
Varity_R
0.040
gMVP
0.29

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs373230856; hg19: chr12-70004478; API