1-219211603-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_138794.5(LYPLAL1):c.589C>G(p.Leu197Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00289 in 1,613,382 control chromosomes in the GnomAD database, including 112 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.015 (64 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (48 hom.)
• Consequence: LYPLAL1 NM_138794.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.179

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0036166608).
• BP6: Variant 1-219211603-C-G is Benign according to our data. Variant chr1-219211603-C-G is described in ClinVar as [Benign]. Clinvar id is 714102.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LYPLAL1	NM_138794.5	c.589C>G	p.Leu197Val	missense_variant	5/5	ENST00000366928.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LYPLAL1	ENST00000366928.10	c.589C>G	p.Leu197Val	missense_variant	5/5	1	NM_138794.5	P1

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 2283 AN: 152046 Hom.: 63 Cov.: 32

Gnomad AFR AF: 0.0521

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00584

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00907

GnomAD3 exomes AF: 0.00422 AC: 1058 AN: 251004 Hom.: 28 AF XY: 0.00313 AC XY: 424 AN XY: 135662

Gnomad AFR exome AF: 0.0572

Gnomad AMR exome AF: 0.00261

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000159

Gnomad OTH exome AF: 0.00294

GnomAD4 exome AF: 0.00162 AC: 2367 AN: 1461218 Hom.: 48 Cov.: 30 AF XY: 0.00140 AC XY: 1018 AN XY: 726916

Gnomad4 AFR exome AF: 0.0556

Gnomad4 AMR exome AF: 0.00298

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000153

Gnomad4 OTH exome AF: 0.00313

GnomAD4 genome AF: 0.0150 AC: 2288 AN: 152164 Hom.: 64 Cov.: 32 AF XY: 0.0149 AC XY: 1109 AN XY: 74402

Gnomad4 AFR AF: 0.0521

Gnomad4 AMR AF: 0.00583

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00898

Alfa AF: 0.00272 Hom.: 14

Bravo AF: 0.0174

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0529 AC: 233

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00502 AC: 610

Asia WGS AF: 0.00202 AC: 8 AN: 3474

EpiCase AF: 0.000109

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.47
Cadd	Benign	20
Dann	Uncertain	1.0
DEOGEN2	Benign	0.018	T;.
Eigen	Benign	0.019
Eigen_PC	Benign	-0.086
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.85	D;D
MetaRNN	Benign	0.0036	T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.2	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-2.4	N;N
REVEL	Benign	0.12
Sift	Uncertain	0.0090	D;D
Sift4G	Benign	0.061	T;D
Polyphen		0.93	P;D
Vest4		0.35
MVP		0.33
MPC		0.0070
ClinPred		0.032	T
GERP RS		2.3
Varity_R		0.65
gMVP		0.50

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: rs34201999; hg19: chr1-219384945;