19-43797763-G-C

Variant summary

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

The NM_001031749.3(LYPD5):c.584C>G(p.Thr195Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LYPD5 NM_001031749.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.189

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=0.13448241).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LYPD5	NM_001031749.3	c.584C>G	p.Thr195Ser	missense_variant	5/5	ENST00000377950.8
LYPD5	NM_001288763.2	c.455C>G	p.Thr152Ser	missense_variant	4/4
LYPD5	NM_182573.3	c.455C>G	p.Thr152Ser	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LYPD5	ENST00000377950.8	c.584C>G	p.Thr195Ser	missense_variant	5/5	1	NM_001031749.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461792 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727218

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

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 16, 2024

The c.584C>G (p.T195S) alteration is located in exon 5 (coding exon 5) of the LYPD5 gene. This alteration results from a C to G substitution at nucleotide position 584, causing the threonine (T) at amino acid position 195 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	Benign	0.10
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
Cadd	Benign	14
Dann	Uncertain	0.97
DEOGEN2	Benign	0.0056	T;.;.
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.49	T;.;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.5	L;.;.
MutationTaster	Benign	0.98	N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.5	N;N;.
REVEL	Benign	0.051
Sift	Benign	0.23	T;T;.
Sift4G	Benign	0.21	T;T;T
Polyphen		0.19	B;.;.
Vest4		0.046
MutPred		0.43		Gain of disorder (P = 0.0864);.;.;
MVP		0.63
MPC		0.27
ClinPred		0.13	T
GERP RS		2.8
Varity_R		0.077
gMVP		0.14

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

LitVar

Other links and lift over

dbSNP: rs1279654253; hg19: chr19-44301915;