NM_173506.7:c.652G>A

Variant names:

• chr19-41837232-C-T
• NM_173506.7:c.652G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173506.7(LYPD4):​c.652G>A​(p.Glu218Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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)
• Consequence: LYPD4 NM_173506.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.531
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.113143384).

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.652G>A	p.Glu218Lys	missense	Exon 5 of 5	NP_775777.3
	LYPD4	NM_001291419.2		c.547G>A	p.Glu183Lys	missense	Exon 5 of 5	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.652G>A	p.Glu218Lys	missense	Exon 5 of 5	ENSP00000476510.1	Q6UWN0-1
	LYPD4	ENST00000343055.5	TSL:1	c.547G>A	p.Glu183Lys	missense	Exon 5 of 5	ENSP00000339568.4	Q6UWN0-2
	LYPD4	ENST00000601246.5	TSL:5	c.547G>A	p.Glu183Lys	missense	Exon 6 of 6	ENSP00000472570.1	Q6UWN0-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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	0.17
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0040	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.53
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.054
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.034	D
Polyphen		0.70	P
Vest4		0.37
MutPred		0.52		Loss of ubiquitination at K219 (P = 0.0262)
MVP		0.061
ClinPred		0.89	D
GERP RS		2.2
Varity_R		0.13
gMVP		0.48
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

hg19: chr19-42341306; COSMIC: COSV58028137; COSMIC: COSV58028137;