NM_152892.3:c.700C>T

Variant summary

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

The NM_152892.3(LRWD1):​c.700C>T​(p.Arg234Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,456,682 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 (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

LRWD1
NM_152892.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.55
Variant links:
Genes affected
LRWD1 (HGNC:21769): (leucine rich repeats and WD repeat domain containing 1) The protein encoded by this gene interacts with components of the origin recognition complex (ORC) and regulates the formation of the prereplicative complex. The encoded protein stabilizes the ORC and therefore aids in DNA replication. This protein is required for the G1/S phase transition of the cell cycle. In addition, the encoded protein binds to trimethylated histone H3 in heterochromatin and recruits the ORC and lysine methyltransferases, which help maintain the repressive heterochromatic state. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

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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=0.13031128).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LRWD1NM_152892.3 linkc.700C>T p.Arg234Trp missense_variant Exon 6 of 15 ENST00000292616.10 NP_690852.1 Q9UFC0A0A140VJD0
LRWD1NM_001317721.2 linkc.244C>T p.Arg82Trp missense_variant Exon 6 of 15 NP_001304650.1 Q9UFC0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LRWD1ENST00000292616.10 linkc.700C>T p.Arg234Trp missense_variant Exon 6 of 15 1 NM_152892.3 ENSP00000292616.5 Q9UFC0

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000825
AC:
2
AN:
242374
Hom.:
0
AF XY:
0.00000757
AC XY:
1
AN XY:
132160
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000550
Gnomad SAS exome
AF:
0.0000329
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1456682
Hom.:
0
Cov.:
33
AF XY:
0.00000276
AC XY:
2
AN XY:
724904
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 05, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.700C>T (p.R234W) alteration is located in exon 6 (coding exon 6) of the LRWD1 gene. This alteration results from a C to T substitution at nucleotide position 700, causing the arginine (R) at amino acid position 234 to be replaced by a tryptophan (W). 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
0.11
BayesDel_addAF
Benign
0.0017
T
BayesDel_noAF
Benign
-0.13
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0074
T;.
Eigen
Benign
-0.30
Eigen_PC
Benign
-0.27
FATHMM_MKL
Benign
0.54
D
LIST_S2
Benign
0.84
T;T
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.13
T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Uncertain
2.1
M;.
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-1.6
N;.
REVEL
Benign
0.20
Sift
Benign
0.14
T;.
Sift4G
Benign
0.095
T;T
Polyphen
0.18
B;.
Vest4
0.36
MutPred
0.30
Gain of catalytic residue at L232 (P = 0.0143);.;
MVP
0.62
MPC
0.065
ClinPred
0.25
T
GERP RS
2.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.064
gMVP
0.54

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs781715136; hg19: chr7-102108530; COSMIC: COSV52960371; COSMIC: COSV52960371; API