1-219211495-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_138794.5(LYPLAL1):c.481C>T(p.Leu161Phe) 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. 12/21 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)
• Consequence: LYPLAL1 NM_138794.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.458

Genes affected

LYPLAL1 (HGNC:20440): (lysophospholipase like 1) Predicted to enable carboxylic ester hydrolase activity and palmitoyl-(protein) hydrolase activity. Predicted to be involved in protein depalmitoylation. Predicted to act upstream of or within negative regulation of Golgi to plasma membrane protein transport. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30430502).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LYPLAL1	NM_138794.5	c.481C>T	p.Leu161Phe	missense_variant	5/5	ENST00000366928.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LYPLAL1	ENST00000366928.10	c.481C>T	p.Leu161Phe	missense_variant	5/5	1	NM_138794.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

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

Jul 22, 2022

The c.481C>T (p.L161F) alteration is located in exon 5 (coding exon 5) of the LYPLAL1 gene. This alteration results from a C to T substitution at nucleotide position 481, causing the leucine (L) at amino acid position 161 to be replaced by a phenylalanine (F). 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	Uncertain	0.47
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Benign	0.045	T;.
Eigen	Benign	0.091
Eigen_PC	Benign	-0.033
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Benign	0.17
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.031	D;D
Polyphen		1.0	D;D
Vest4		0.28
MutPred		0.34		Gain of ubiquitination at K163 (P = 0.1181);.;
MVP		0.40
MPC		0.010
ClinPred		0.98	D
GERP RS		3.2
Varity_R		0.81
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr1-219384837;