19-41837256-C-G

Variant names:

• chr19-41837256-C-G
• NM_173506.7:c.628G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_173506.7(LYPD4):​c.628G>C​(p.Val210Leu) 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. 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: 2.98
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41167176).

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.628G>C	p.Val210Leu	missense	Exon 5 of 5	NP_775777.3
	LYPD4	NM_001291419.2		c.523G>C	p.Val175Leu	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.628G>C	p.Val210Leu	missense	Exon 5 of 5	ENSP00000476510.1	Q6UWN0-1
	LYPD4	ENST00000343055.5	TSL:1	c.523G>C	p.Val175Leu	missense	Exon 5 of 5	ENSP00000339568.4	Q6UWN0-2
	LYPD4	ENST00000601246.5	TSL:5	c.523G>C	p.Val175Leu	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	Pathogenic	0.61
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.026	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.41	T
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.0
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.36
Sift	Benign	0.12	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.83	P
Vest4		0.60
MutPred		0.54		Gain of catalytic residue at V210 (P = 0.0801)
MVP		0.22
ClinPred		0.95	D
GERP RS		4.4
Varity_R		0.14
gMVP		0.56
Mutation Taster		=100/0	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: chr19-42341330;