10-132344639-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_030626.3(LRRC27):ā€‹c.542C>Gā€‹(p.Pro181Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,613,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00020 ( 0 hom., cov: 33)
Exomes š‘“: 0.000024 ( 0 hom. )

Consequence

LRRC27
NM_030626.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.235
Variant links:
Genes affected
LRRC27 (HGNC:29346): (leucine rich repeat containing 27)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.02126795).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LRRC27NM_030626.3 linkuse as main transcriptc.542C>G p.Pro181Arg missense_variant 5/11 ENST00000368614.8 NP_085129.1 Q9C0I9-1A0A140VJN2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LRRC27ENST00000368614.8 linkuse as main transcriptc.542C>G p.Pro181Arg missense_variant 5/111 NM_030626.3 ENSP00000357603.3 Q9C0I9-1

Frequencies

GnomAD3 genomes
AF:
0.000204
AC:
31
AN:
152190
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000748
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
GnomAD3 exomes
AF:
0.0000875
AC:
22
AN:
251328
Hom.:
0
AF XY:
0.0000515
AC XY:
7
AN XY:
135846
show subpopulations
Gnomad AFR exome
AF:
0.000861
Gnomad AMR exome
AF:
0.000232
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:
0.0000239
AC:
35
AN:
1461518
Hom.:
0
Cov.:
30
AF XY:
0.0000206
AC XY:
15
AN XY:
727034
show subpopulations
Gnomad4 AFR exome
AF:
0.000568
Gnomad4 AMR exome
AF:
0.000179
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.000204
AC:
31
AN:
152308
Hom.:
0
Cov.:
33
AF XY:
0.000148
AC XY:
11
AN XY:
74480
show subpopulations
Gnomad4 AFR
AF:
0.000746
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
Alfa
AF:
0.0000756
Hom.:
0
Bravo
AF:
0.000276
ESP6500AA
AF:
0.000681
AC:
3
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000906
AC:
11

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 20, 2023The c.542C>G (p.P181R) alteration is located in exon 5 (coding exon 4) of the LRRC27 gene. This alteration results from a C to G substitution at nucleotide position 542, causing the proline (P) at amino acid position 181 to be replaced by an arginine (R). 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
0.081
BayesDel_addAF
Benign
-0.55
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
0.81
DANN
Benign
0.96
DEOGEN2
Benign
0.037
.;.;T;T;.
Eigen
Benign
-0.96
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.082
N
LIST_S2
Benign
0.69
T;T;.;T;T
M_CAP
Benign
0.0032
T
MetaRNN
Benign
0.021
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L;L;L;L;.
PrimateAI
Benign
0.20
T
PROVEAN
Benign
-1.7
N;.;N;N;N
REVEL
Benign
0.041
Sift
Benign
0.086
T;.;T;T;T
Sift4G
Benign
0.45
T;T;T;T;T
Polyphen
0.91
P;P;P;P;P
Vest4
0.20
MVP
0.16
MPC
0.39
ClinPred
0.029
T
GERP RS
-3.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.036
gMVP
0.31

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
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: rs149563961; hg19: chr10-134158143; API