Genetic Variant LYPD4:p.Arg108His (chr19-41838150-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_173506.7(LYPD4):c.323G>A(p.Arg108His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000701 in 1,612,052 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 0.000039 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

LYPD4
NM_173506.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00500

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 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=0.08725193).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYPD4	NM_173506.7 link	c.323G>A	p.Arg108His	missense_variant	Exon 4 of 5	ENST00000609812.6	NP_775777.3	Q6UWN0-1A8K8E0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LYPD4	ENST00000609812.6 link	c.323G>A	p.Arg108His	missense_variant	Exon 4 of 5	1	NM_173506.7	ENSP00000476510.1	Q6UWN0-1
LYPD4	ENST00000343055.5 link	c.218G>A	p.Arg73His	missense_variant	Exon 4 of 5	1		ENSP00000339568.4	Q6UWN0-2
LYPD4	ENST00000601246.5 link	c.218G>A	p.Arg73His	missense_variant	Exon 5 of 6	5		ENSP00000472570.1	Q6UWN0-2

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000240

AC:

AN:

250300

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

135280

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000733

AC:

107

AN:

1459974

Hom.:

Cov.:

AF XY:

0.0000785

AC XY:

AN XY:

726082

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000672

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000909

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000395

AC:

AN:

152078

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.323G>A (p.R108H) alteration is located in exon 4 (coding exon 3) of the LYPD4 gene. This alteration results from a G to A substitution at nucleotide position 323, causing the arginine (R) at amino acid position 108 to be replaced by a histidine (H). 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

0.074

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0034

.;T;.

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.77

T;T;.

M_CAP

Benign

0.0042

MetaRNN

Benign

0.087

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.72

.;N;.

PrimateAI

Benign

0.40

PROVEAN

Benign

0.46

N;.;.

REVEL

Benign

0.011

Sift

Benign

0.27

T;.;.

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.0090

B;B;B

Vest4

0.24

MutPred

0.42

.;Loss of helix (P = 0.1299);.;

MVP

0.030

ClinPred

0.063

GERP RS

0.16

Varity_R

0.070

gMVP

0.31

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.

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