NM_152892.3:c.52G>T

Variant names:

• chr7-102465132-G-T
• rs761307074
• NM_152892.3:c.52G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152892.3(LRWD1):​c.52G>T​(p.Asp18Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000732 in 1,366,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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: 7.3e-7 (0 hom.)
• Consequence: LRWD1 NM_152892.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.375
• Publications: 0 publications found

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]

ACMG classification

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=0.20047602).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152892.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRWD1	NM_152892.3	MANE Select	c.52G>T	p.Asp18Tyr	missense	Exon 1 of 15	NP_690852.1	Q9UFC0
	LRWD1	NM_001317721.2		c.-423G>T		5_prime_UTR	Exon 1 of 15	NP_001304650.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRWD1	ENST00000292616.10	TSL:1 MANE Select	c.52G>T	p.Asp18Tyr	missense	Exon 1 of 15	ENSP00000292616.5	Q9UFC0
	LRWD1	ENST00000896262.1		c.52G>T	p.Asp18Tyr	missense	Exon 1 of 16	ENSP00000566321.1
	LRWD1	ENST00000922655.1		c.52G>T	p.Asp18Tyr	missense	Exon 1 of 15	ENSP00000592714.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.32e-7 AC: 1 AN: 1366842 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 675824

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 27982

American (AMR) AF: 0.00 AC: 0 AN: 28712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23618

East Asian (EAS) AF: 0.00 AC: 0 AN: 30968

South Asian (SAS) AF: 0.0000133 AC: 1 AN: 74930

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48670

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5536

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1070102

Other (OTH) AF: 0.00 AC: 0 AN: 56324

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.046	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.0085	T
Eigen	Benign	-0.024
Eigen_PC	Benign	-0.014
FATHMM_MKL	Benign	0.63	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.080	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.38
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.15
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.039	D
Polyphen		0.93	P
Vest4		0.26
MutPred		0.30		Gain of MoRF binding (P = 0.056)
MVP		0.74
MPC		3.1
ClinPred		0.63	D
GERP RS		3.0
PromoterAI		-0.0070	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.092
gMVP		0.46
Mutation Taster		=88/12	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

Other links and lift over

dbSNP: rs761307074; hg19: chr7-102105579;