11-76659827-C-T

Variant summary

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

The NM_001128922.2(LRRC32):​c.1766G>A​(p.Arg589His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 1,614,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. R589G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

LRRC32
NM_001128922.2 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.40
Variant links:
Genes affected
LRRC32 (HGNC:4161): (leucine rich repeat containing 32) This gene encodes a type I membrane protein which contains 20 leucine-rich repeats. Alterations in the chromosomal region 11q13-11q14 are involved in several pathologies. [provided by RefSeq, Jul 2008]

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=0.15997306).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LRRC32NM_001128922.2 linkc.1766G>A p.Arg589His missense_variant Exon 3 of 3 ENST00000260061.9 NP_001122394.1 Q14392A0A024R5J7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LRRC32ENST00000260061.9 linkc.1766G>A p.Arg589His missense_variant Exon 3 of 3 1 NM_001128922.2 ENSP00000260061.5 Q14392

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152238
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000479
AC:
12
AN:
250484
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135520
show subpopulations
Gnomad AFR exome
AF:
0.0000620
Gnomad AMR exome
AF:
0.0000579
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000382
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000233
AC:
34
AN:
1461770
Hom.:
0
Cov.:
31
AF XY:
0.0000138
AC XY:
10
AN XY:
727186
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000302
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000126
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152356
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74508
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000340
ExAC
AF:
0.0000412
AC:
5
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 03, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1766G>A (p.R589H) alteration is located in exon 3 (coding exon 2) of the LRRC32 gene. This alteration results from a G to A substitution at nucleotide position 1766, causing the arginine (R) at amino acid position 589 to be replaced by a histidine (H). 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
Benign
0.083
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.034
T;T;T
Eigen
Benign
0.11
Eigen_PC
Benign
0.090
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.74
.;T;.
M_CAP
Benign
0.0084
T
MetaRNN
Benign
0.16
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.0
L;L;L
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-0.81
N;N;N
REVEL
Benign
0.085
Sift
Benign
0.054
T;T;T
Sift4G
Uncertain
0.045
D;D;D
Polyphen
1.0
D;D;D
Vest4
0.067
MutPred
0.38
Loss of methylation at R589 (P = 0.1199);Loss of methylation at R589 (P = 0.1199);Loss of methylation at R589 (P = 0.1199);
MVP
0.86
MPC
0.21
ClinPred
0.096
T
GERP RS
4.6
Varity_R
0.13
gMVP
0.79

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

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

Other links and lift over

dbSNP: rs565593386; hg19: chr11-76370871; API