NM_138794.5:c.481C>T

Variant names:

• chr1-219211495-C-T
• NM_138794.5:c.481C>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/22 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138794.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYPLAL1	NM_138794.5	MANE Select	c.481C>T	p.Leu161Phe	missense	Exon 5 of 5	NP_620149.2	Q5VWZ2-1
	LYPLAL1	NM_001350628.2		c.508C>T	p.Leu170Phe	missense	Exon 6 of 6	NP_001337557.1
	LYPLAL1	NM_001350629.2		c.460C>T	p.Leu154Phe	missense	Exon 6 of 6	NP_001337558.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYPLAL1	ENST00000366928.10	TSL:1 MANE Select	c.481C>T	p.Leu161Phe	missense	Exon 5 of 5	ENSP00000355895.5	Q5VWZ2-1
	LYPLAL1	ENST00000366927.3	TSL:1	c.433C>T	p.Leu145Phe	missense	Exon 5 of 5	ENSP00000355894.3	Q5VWZ2-2
	LYPLAL1	ENST00000474379.5	TSL:1	n.292C>T		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.46
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.17
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.031	D
Polyphen		1.0	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
Mutation Taster		=66/34	polymorphism

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

Other links and lift over

hg19: chr1-219384837;