19-18396300-C-G

Variant summary

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

The NM_145256.3(LRRC25):​c.664G>C​(p.Gly222Arg) 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 1,461,470 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. 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. G222S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

LRRC25
NM_145256.3 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0460
Variant links:
Genes affected
LRRC25 (HGNC:29806): (leucine rich repeat containing 25) Predicted to be located in cytoplasm. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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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=0.07903832).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LRRC25NM_145256.3 linkc.664G>C p.Gly222Arg missense_variant Exon 1 of 2 ENST00000339007.4 NP_660299.2 Q8N386
LRRC25XM_005259739.5 linkc.664G>C p.Gly222Arg missense_variant Exon 2 of 3 XP_005259796.1 Q8N386

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LRRC25ENST00000339007.4 linkc.664G>C p.Gly222Arg missense_variant Exon 1 of 2 1 NM_145256.3 ENSP00000340983.2 Q8N386
LRRC25ENST00000595840.1 linkc.664G>C p.Gly222Arg missense_variant Exon 2 of 3 1 ENSP00000472290.1 Q8N386

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461470
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727030
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.29
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
9.0
DANN
Benign
0.95
DEOGEN2
Benign
0.020
T;T
Eigen
Benign
-0.61
Eigen_PC
Benign
-0.68
FATHMM_MKL
Benign
0.31
N
LIST_S2
Benign
0.64
.;T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.079
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.1
L;L
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-0.55
N;.
REVEL
Benign
0.074
Sift
Uncertain
0.021
D;.
Sift4G
Uncertain
0.040
D;D
Polyphen
0.87
P;P
Vest4
0.17
MutPred
0.15
Gain of methylation at G222 (P = 0.0314);Gain of methylation at G222 (P = 0.0314);
MVP
0.043
MPC
0.66
ClinPred
0.22
T
GERP RS
1.8
Varity_R
0.12
gMVP
0.37

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: rs771155177; hg19: chr19-18507110; API