Variant 7-102465127-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_152892.3(LRWD1):c.47A>G(p.Lys16Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000191 in 1,519,714 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: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

LRWD1
NM_152892.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.180

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]

LRWD1 links:

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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=0.07133183).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRWD1	NM_152892.3 linkuse as main transcript	c.47A>G	p.Lys16Arg	missense_variant	1/15	ENST00000292616.10	NP_690852.1
LRWD1	NM_001317721.2 linkuse as main transcript	c.-428A>G		5_prime_UTR_variant	1/15		NP_001304650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRWD1	ENST00000292616.10 linkuse as main transcript	c.47A>G	p.Lys16Arg	missense_variant	1/15	1	NM_152892.3	ENSP00000292616	P1

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

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:

0.000478

GnomAD3 exomes

AF:

0.00000764

AC:

AN:

130916

Hom.:

AF XY:

0.00

AC XY:

AN XY:

74590

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000336

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1367500

Hom.:

Cov.:

AF XY:

0.0000118

AC XY:

AN XY:

676112

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000346

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000323

Gnomad4 SAS exome

AF:

0.0000133

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000747

Gnomad4 OTH exome

AF:

0.0000710

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000785

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:

0.000478

Bravo

AF:

0.000155

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 submitter

clinical testing

Ambry Genetics

Oct 20, 2023

The c.47A>G (p.K16R) alteration is located in exon 1 (coding exon 1) of the LRWD1 gene. This alteration results from a A to G substitution at nucleotide position 47, causing the lysine (K) at amino acid position 16 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

0.070

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.0075

T;.

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.64

T;T

M_CAP

Benign

0.0052

MetaRNN

Benign

0.071

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;.

MutationTaster

Benign

0.95

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.3

N;.

REVEL

Benign

0.11

Sift

Benign

0.084

T;.

Sift4G

Benign

0.12

T;D

Polyphen

0.027

B;.

Vest4

0.11

MutPred

0.15

Loss of ubiquitination at K16 (P = 0.0309);Loss of ubiquitination at K16 (P = 0.0309);

MVP

0.35

MPC

1.4

ClinPred

0.41

GERP RS

1.0

Varity_R

0.076

gMVP

0.24

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over