Genetic Variant LYPD4:p.Val109Leu (chr19-41838148-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_173506.7(LYPD4):c.325G>C(p.Val109Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000158 in 1,612,558 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 1 hom. )

Consequence

LYPD4
NM_173506.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0240

Publications

1 publications found

Variant links:

Genes affected

LYPD4 (HGNC:28659): (LY6/PLAUR domain containing 4) Predicted to be located in extracellular region and plasma membrane. Predicted to be active in plasma membrane raft. Predicted to be anchored component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

LYPD4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12009579).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173506.7. 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
	LYPD4	NM_173506.7	MANE Select	c.325G>C	p.Val109Leu	missense	Exon 4 of 5	NP_775777.3
	LYPD4	NM_001291419.2		c.220G>C	p.Val74Leu	missense	Exon 4 of 5	NP_001278348.1	Q6UWN0-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LYPD4	ENST00000609812.6	TSL:1 MANE Select	c.325G>C	p.Val109Leu	missense	Exon 4 of 5	ENSP00000476510.1	Q6UWN0-1
LYPD4	ENST00000343055.5	TSL:1	c.220G>C	p.Val74Leu	missense	Exon 4 of 5	ENSP00000339568.4	Q6UWN0-2
LYPD4	ENST00000601246.5	TSL:5	c.220G>C	p.Val74Leu	missense	Exon 5 of 6	ENSP00000472570.1	Q6UWN0-2

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000216

AC:

AN:

250506

AF XY:

0.000229

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 FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.000441

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000162

AC:

237

AN:

1460442

Hom.:

Cov.:

AF XY:

0.000154

AC XY:

112

AN XY:

726374

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33450

American (AMR)

AF:

0.0000224

AC:

AN:

44642

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26094

East Asian (EAS)

AF:

0.00

AC:

AN:

39640

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86136

European-Finnish (FIN)

AF:

0.000356

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.000190

AC:

211

AN:

1110994

Other (OTH)

AF:

0.0000829

AC:

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000118

AC:

AN:

152116

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41430

American (AMR)

AF:

0.000328

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0000944

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68024

Other (OTH)

AF:

0.000478

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000339

Hom.:

Bravo

AF:

0.000147

ExAC

AF:

0.000313

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.50

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.022

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.77

M_CAP

Benign

0.0072

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

PhyloP100

0.024

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.1

REVEL

Benign

0.053

Sift

Uncertain

0.015

Sift4G

Uncertain

0.037

Polyphen

0.87

Vest4

0.48

MutPred

0.63

Loss of catalytic residue at V109 (P = 0.0676)

MVP

0.072

ClinPred

0.076

GERP RS

-0.44

Varity_R

0.034

gMVP

0.25

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over