19-43798983-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001031749.3(LYPD5):c.199C>A(p.Arg67Ser) 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LYPD5 NM_001031749.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.10

Genes affected

LYPD5 (HGNC:26397): (LY6/PLAUR domain containing 5) Predicted to be located in extracellular region. Predicted to be active in 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=0.22192219).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LYPD5	NM_001031749.3	c.199C>A	p.Arg67Ser	missense_variant	3/5	ENST00000377950.8
LYPD5	NM_001288763.2	c.70C>A	p.Arg24Ser	missense_variant	2/4
LYPD5	NM_182573.3	c.70C>A	p.Arg24Ser	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LYPD5	ENST00000377950.8	c.199C>A	p.Arg67Ser	missense_variant	3/5	1	NM_001031749.3	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1417370 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 700814

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 29, 2024

The c.199C>A (p.R67S) alteration is located in exon 3 (coding exon 3) of the LYPD5 gene. This alteration results from a C to A substitution at nucleotide position 199, causing the arginine (R) at amino acid position 67 to be replaced by a serine (S). 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	Pathogenic	0.87
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
Cadd	Uncertain	25
Dann	Uncertain	0.99
DEOGEN2	Benign	0.0045	T;.;.;.;.
Eigen	Uncertain	0.28
Eigen_PC	Benign	0.22
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.72	T;.;T;T;T
M_CAP	Benign	0.083	D
MetaRNN	Benign	0.22	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M;.;.;.;.
MutationTaster	Benign	0.88	N;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.2	N;N;.;.;.
REVEL	Benign	0.14
Sift	Benign	0.14	T;D;.;.;.
Sift4G	Uncertain	0.014	D;D;D;.;.
Polyphen		1.0	D;.;.;.;.
Vest4		0.34
MutPred		0.42		Loss of MoRF binding (P = 0.0771);.;.;.;.;
MVP		0.52
MPC		0.39
ClinPred		0.80	D
GERP RS		2.0
Varity_R		0.21
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: chr19-44303135;