chr1-219193093-C-T

Variant names:

• chr1-219193093-C-T
• rs769337337
• NM_138794.5:c.203C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_138794.5(LYPLAL1):​c.203C>T​(p.Pro68Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000005 in 1,598,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: LYPLAL1 NM_138794.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.03
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.793

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.203C>T	p.Pro68Leu	missense	Exon 3 of 5	NP_620149.2	Q5VWZ2-1
	LYPLAL1	NM_001350628.2		c.230C>T	p.Pro77Leu	missense	Exon 4 of 6	NP_001337557.1
	LYPLAL1	NM_001300771.2		c.89C>T	p.Pro30Leu	missense	Exon 3 of 5	NP_001287700.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYPLAL1	ENST00000366928.10	TSL:1 MANE Select	c.203C>T	p.Pro68Leu	missense	Exon 3 of 5	ENSP00000355895.5	Q5VWZ2-1
	LYPLAL1	ENST00000366927.3	TSL:1	c.192-37C>T		intron	N/A	ENSP00000355894.3	Q5VWZ2-2
	LYPLAL1	ENST00000474379.5	TSL:1	n.155+13847C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000133 AC: 2 AN: 150444 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000488

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000121 AC: 3 AN: 247994 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000414 AC: 6 AN: 1448260 Hom.: 0 Cov.: 33 AF XY: 0.00000139 AC XY: 1 AN XY: 720662

African (AFR) AF: 0.00 AC: 0 AN: 33082

American (AMR) AF: 0.00 AC: 0 AN: 44292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25650

East Asian (EAS) AF: 0.0000255 AC: 1 AN: 39216

South Asian (SAS) AF: 0.00 AC: 0 AN: 85712

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52208

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5684

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102854

Other (OTH) AF: 0.0000839 AC: 5 AN: 59562

GnomAD4 genome AF: 0.0000133 AC: 2 AN: 150444 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 73322

African (AFR) AF: 0.0000488 AC: 2 AN: 40966

American (AMR) AF: 0.00 AC: 0 AN: 15074

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3444

East Asian (EAS) AF: 0.00 AC: 0 AN: 5136

South Asian (SAS) AF: 0.00 AC: 0 AN: 4788

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67406

Other (OTH) AF: 0.00 AC: 0 AN: 2068

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000824 AC: 1

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	0.37
BayesDel_addAF	Benign	-0.0073	T
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.051	T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.031	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.86	L
PhyloP100		6.0
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-8.9	D
REVEL	Uncertain	0.41
Sift	Benign	0.095	T
Sift4G	Benign	0.61	T
Polyphen		0.91	P
Vest4		0.84
MutPred		0.51		Loss of disorder (P = 0.0078)
MVP		0.33
MPC		0.0062
ClinPred		0.94	D
GERP RS		5.5
Varity_R		0.73
gMVP		0.72
Mutation Taster		=9/91	disease causing

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

dbSNP: rs769337337; hg19: chr1-219366435;