dbSNP rs1555831418: LYPD4:p.Tyr94Cys (chr19-41838192-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_173506.7(LYPD4):c.281A>G(p.Tyr94Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000817 in 1,591,606 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

LYPD4
NM_173506.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.00

Publications

0 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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.281A>G	p.Tyr94Cys	missense	Exon 4 of 5	NP_775777.3
	LYPD4	NM_001291419.2		c.176A>G	p.Tyr59Cys	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.281A>G	p.Tyr94Cys	missense	Exon 4 of 5	ENSP00000476510.1	Q6UWN0-1
LYPD4	ENST00000343055.5	TSL:1	c.176A>G	p.Tyr59Cys	missense	Exon 4 of 5	ENSP00000339568.4	Q6UWN0-2
LYPD4	ENST00000601246.5	TSL:5	c.176A>G	p.Tyr59Cys	missense	Exon 5 of 6	ENSP00000472570.1	Q6UWN0-2

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152016

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD2 exomes

AF:

0.00000425

AC:

AN:

235250

AF XY:

0.00000786

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:

0.00

Gnomad NFE exome

AF:

0.00000931

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000834

AC:

AN:

1439590

Hom.:

Cov.:

AF XY:

0.0000112

AC XY:

AN XY:

713894

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32740

American (AMR)

AF:

0.00

AC:

AN:

41824

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24798

East Asian (EAS)

AF:

0.00

AC:

AN:

39284

South Asian (SAS)

AF:

0.00

AC:

AN:

84040

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52814

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5628

European-Non Finnish (NFE)

AF:

0.0000109

AC:

AN:

1099116

Other (OTH)

AF:

0.00

AC:

AN:

59346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152016

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41380

American (AMR)

AF:

0.00

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67992

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

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

Pathogenic

0.76

BayesDel_addAF

Uncertain

0.019

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.028

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.85

M_CAP

Benign

0.032

MetaRNN

Uncertain

0.69

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.6

PhyloP100

3.0

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.17

Sift

Benign

0.11

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.79

MutPred

0.41

Loss of phosphorylation at Y94 (P = 0.0453)

MVP

0.055

ClinPred

0.94

GERP RS

4.0

Varity_R

0.12

gMVP

0.42

Mutation Taster

=98/2

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over