chr1-23794448-G-T

Variant names:

• chr1-23794448-G-T
• NM_007260.3:c.493G>T

Variant summary

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

The NM_007260.3(LYPLA2):​c.493G>T​(p.Asp165Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,800 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D165N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: LYPLA2 NM_007260.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.51

Genes affected

LYPLA2 (HGNC:6738): (lysophospholipase 2) Lysophospholipases are enzymes that act on biological membranes to regulate the multifunctional lysophospholipids. There are alternatively spliced transcript variants described for this gene but the full length nature is not known yet. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYPLA2	NM_007260.3	c.493G>T	p.Asp165Tyr	missense_variant	Exon 9 of 10	ENST00000374514.8	NP_009191.1
LYPLA2	XM_005245728.6	c.529G>T	p.Asp177Tyr	missense_variant	Exon 9 of 10		XP_005245785.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LYPLA2	ENST00000374514.8	c.493G>T	p.Asp165Tyr	missense_variant	Exon 9 of 10	1	NM_007260.3	ENSP00000363638.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461800 Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3 AN XY: 727202

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;T;T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.50	D;D;D
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.8	M;.;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-5.0	D;D;D
REVEL	Benign	0.17
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.017	D;D;D
Polyphen		0.14	B;.;.
Vest4		0.27
MutPred		0.48		Loss of ubiquitination at K164 (P = 0.0387);.;.;
MVP		0.23
MPC		0.84
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.90
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: chr1-24120938;