GeneBe

NM_001378102.1:c.373G>T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 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. 16/22 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

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.617

Publications

0 publications found
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]
WDFY4 Gene-Disease associations (from GenCC):
  • complex neurodevelopmental disorder
    Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.072551966).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378102.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
LRRC18
NM_001378102.1
MANE Select
c.373G>Tp.Ala125Ser
missense
Exon 3 of 4NP_001365031.1Q8N456-1
WDFY4
NM_001394531.1
MANE Select
c.7586+11920C>A
intron
N/ANP_001381460.1Q6ZS81-1
LRRC18
NM_001006939.4
c.373G>Tp.Ala125Ser
missense
Exon 2 of 3NP_001006940.3Q8N456-1

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
LRRC18
ENST00000374160.8
TSL:1 MANE Select
c.373G>Tp.Ala125Ser
missense
Exon 3 of 4ENSP00000363275.3Q8N456-1
WDFY4
ENST00000325239.12
TSL:5 MANE Select
c.7586+11920C>A
intron
N/AENSP00000320563.5Q6ZS81-1
WDFY4
ENST00000858472.1
c.7586+11920C>A
intron
N/AENSP00000528531.1

Frequencies

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
PhyloP100
0.62
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
PromoterAI
0.019
Neutral
Varity_R
0.039
gMVP
0.28
Mutation Taster
=98/2
polymorphism

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

Other links and lift over

dbSNP: rs776174712; hg19: chr10-50121828; API