rs776174712

Variant summary

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

The NM_001378102.1(LRRC18):​c.373G>T​(p.Ala125Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. A125T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

LRRC18
NM_001378102.1 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.617
Variant links:
Genes affected
LRRC18 (HGNC:23199): (leucine rich repeat containing 18) Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]
WDFY4 (HGNC:29323): (WDFY family member 4) Predicted to be involved in autophagy. Predicted to act upstream of or within with a positive effect on CD8-positive, alpha-beta T cell activation. Predicted to act upstream of or within antigen processing and presentation and cellular response to virus. Predicted to be located in early endosome and endoplasmic reticulum. [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=0.072551966).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LRRC18NM_001378102.1 linkc.373G>T p.Ala125Ser missense_variant Exon 3 of 4 ENST00000374160.8 NP_001365031.1
WDFY4NM_001394531.1 linkc.7586+11920C>A intron_variant Intron 47 of 61 ENST00000325239.12 NP_001381460.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LRRC18ENST00000374160.8 linkc.373G>T p.Ala125Ser missense_variant Exon 3 of 4 1 NM_001378102.1 ENSP00000363275.3 Q8N456-1
WDFY4ENST00000325239.12 linkc.7586+11920C>A intron_variant Intron 47 of 61 5 NM_001394531.1 ENSP00000320563.5 Q6ZS81-1
ENSG00000241577ENST00000430438.1 linkn.173+18703G>T intron_variant Intron 2 of 2 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
62
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.74
CADD
Benign
10
DANN
Benign
0.91
DEOGEN2
Benign
0.0043
T
Eigen
Benign
-0.98
Eigen_PC
Benign
-0.86
FATHMM_MKL
Benign
0.085
N
LIST_S2
Benign
0.073
T
M_CAP
Benign
0.0059
T
MetaRNN
Benign
0.073
T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
-0.29
N
PrimateAI
Benign
0.47
T
PROVEAN
Benign
0.30
N
REVEL
Benign
0.034
Sift
Benign
0.46
T
Sift4G
Benign
0.43
T
Polyphen
0.0
B
Vest4
0.034
MutPred
0.31
Gain of disorder (P = 0.0913);
MVP
0.088
MPC
0.014
ClinPred
0.14
T
GERP RS
3.6
Varity_R
0.039
gMVP
0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-50121828; API