19-41838913-C-T

Variant names:

• chr19-41838913-C-T
• rs200441266
• NM_173506.7:c.179G>A

Variant summary

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

The NM_173506.7(LYPD4):​c.179G>A​(p.Gly60Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000039 in 1,614,000 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000037 (0 hom.)
• Consequence: LYPD4 NM_173506.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.65
• Publications: 1 publications found

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]

ACMG classification

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.179G>A	p.Gly60Asp	missense	Exon 3 of 5	NP_775777.3
	LYPD4	NM_001291419.2		c.106+267G>A		intron	N/A	NP_001278348.1	Q6UWN0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYPD4	ENST00000609812.6	TSL:1 MANE Select	c.179G>A	p.Gly60Asp	missense	Exon 3 of 5	ENSP00000476510.1	Q6UWN0-1
	LYPD4	ENST00000343055.5	TSL:1	c.106+267G>A		intron	N/A	ENSP00000339568.4	Q6UWN0-2
	LYPD4	ENST00000601246.5	TSL:5	c.106+267G>A		intron	N/A	ENSP00000472570.1	Q6UWN0-2

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152070 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

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: 0.000472

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000835 AC: 21 AN: 251360 AF XY: 0.0000736

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: 0.000556

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.0000369 AC: 54 AN: 1461816 Hom.: 0 Cov.: 36 AF XY: 0.0000330 AC XY: 24 AN XY: 727216

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.000637 AC: 34 AN: 53354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1112004

Other (OTH) AF: 0.0000828 AC: 5 AN: 60396

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152184 Hom.: 0 Cov.: 30 AF XY: 0.0000403 AC XY: 3 AN XY: 74398

African (AFR) AF: 0.00 AC: 0 AN: 41512

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.000472 AC: 5 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68012

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.0000239 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.000132 AC: 16

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	Pathogenic	0.77
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.043	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0086	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.7
PrimateAI	Uncertain	0.52	T
Sift4G	Uncertain	0.053	T
Polyphen		1.0	D
Vest4		0.87
MVP		0.061
ClinPred		0.22	T
GERP RS		2.9
Varity_R		0.085
gMVP		0.73
Mutation Taster		=99/1	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: rs200441266; hg19: chr19-42342987;