7-102467367-C-T

Variant names:

• chr7-102467367-C-T
• rs542708497
• NM_152892.3:c.461C>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.461C>T​(p.Ala154Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,460,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: LRWD1 NM_152892.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.18
• Publications: 1 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=0.1232672).

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.461C>T	p.Ala154Val	missense	Exon 4 of 15	NP_690852.1	Q9UFC0
	LRWD1	NM_001317721.2		c.5C>T	p.Ala2Val	missense	Exon 4 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.461C>T	p.Ala154Val	missense	Exon 4 of 15	ENSP00000292616.5	Q9UFC0
	LRWD1	ENST00000896262.1		c.461C>T	p.Ala154Val	missense	Exon 4 of 16	ENSP00000566321.1
	LRWD1	ENST00000922655.1		c.461C>T	p.Ala154Val	missense	Exon 4 of 15	ENSP00000592714.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000405 AC: 1 AN: 247090 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000898

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000110 AC: 16 AN: 1460090 Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8 AN XY: 726184

African (AFR) AF: 0.00 AC: 0 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44506

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39622

South Asian (SAS) AF: 0.00 AC: 0 AN: 85888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53204

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.0000144 AC: 16 AN: 1111278

Other (OTH) AF: 0.00 AC: 0 AN: 60320

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000468 Hom.: 0

ExAC AF: 0.00000824 AC: 1

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	0.12
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.2
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.012
Sift	Benign	0.28	T
Sift4G	Benign	0.18	T
Polyphen		0.0080	B
Vest4		0.15
MutPred		0.37		Loss of loop (P = 0.0203)
MVP		0.68
MPC		0.054
ClinPred		0.13	T
GERP RS		2.8
Varity_R		0.033
gMVP		0.22
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs542708497; hg19: chr7-102107814;