19-41837232-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/21 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

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

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=0.113143384).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYPD4	NM_173506.7	c.652G>A	p.Glu218Lys	missense_variant	Exon 5 of 5	ENST00000609812.6	NP_775777.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LYPD4	ENST00000609812.6	c.652G>A	p.Glu218Lys	missense_variant	Exon 5 of 5	1	NM_173506.7	ENSP00000476510.1
LYPD4	ENST00000343055.5	c.547G>A	p.Glu183Lys	missense_variant	Exon 5 of 5	1		ENSP00000339568.4
LYPD4	ENST00000601246.5	c.547G>A	p.Glu183Lys	missense_variant	Exon 6 of 6	5		ENSP00000472570.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.652G>A (p.E218K) alteration is located in exon 5 (coding exon 4) of the LYPD4 gene. This alteration results from a G to A substitution at nucleotide position 652, causing the glutamic acid (E) at amino acid position 218 to be replaced by a lysine (K). 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	0.17
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;T;.
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	.;L;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.6	N;.;.
REVEL	Benign	0.054
Sift	Uncertain	0.015	D;.;.
Sift4G	Uncertain	0.034	D;D;D
Polyphen		0.70	P;P;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

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

No publications associated with this variant yet.

Other links and lift over

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