Variant 2-30525696-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001002257.3(LCLAT1):c.106C>T(p.Pro36Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,613,902 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

LCLAT1
NM_001002257.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.96

Variant links:

Genes affected

LCLAT1 (HGNC:26756): (lysocardiolipin acyltransferase 1) Enables 1-acylglycerol-3-phosphate O-acyltransferase activity. Predicted to be involved in phosphatidylinositol acyl-chain remodeling. Located in cytosol and endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

LCLAT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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/exons	MANE	Protein	UniProt
LCLAT1	NM_001002257.3 linkuse as main transcript	c.106C>T	p.Pro36Ser	missense_variant	2/6	ENST00000379509.8	NP_001002257.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LCLAT1	ENST00000379509.8 linkuse as main transcript	c.106C>T	p.Pro36Ser	missense_variant	2/6	1	NM_001002257.3	ENSP00000368823	P1	Q6UWP7-3

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

151940

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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:

0.0000294

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251400

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461844

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000592

AC:

AN:

152058

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000474

Bravo

AF:

0.0000264

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 12, 2023

The c.220C>T (p.P74S) alteration is located in exon 3 (coding exon 2) of the LCLAT1 gene. This alteration results from a C to T substitution at nucleotide position 220, causing the proline (P) at amino acid position 74 to be replaced by a serine (S). 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

0.34

BayesDel_addAF

Uncertain

0.030

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

T;.;.;.;.;.;D;.;.;.

Eigen

Benign

0.048

Eigen_PC

Benign

0.17

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.86

D;D;D;D;D;D;D;D;D;D

M_CAP

Uncertain

0.091

MetaRNN

Uncertain

0.63

D;D;D;D;D;D;D;D;D;D

MetaSVM

Uncertain

0.40

MutationAssessor

Benign

1.7

.;.;.;L;.;.;L;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-5.7

D;D;D;D;D;D;D;D;D;D

REVEL

Uncertain

0.48

Sift

Uncertain

0.018

D;T;T;D;T;T;D;D;D;D

Sift4G

Benign

0.21

T;T;D;D;T;T;D;T;T;T

Polyphen

0.16, 0.30

.;.;.;B;.;.;B;.;.;.

Vest4

0.36, 0.39, 0.36

MutPred

0.47

.;.;.;Gain of MoRF binding (P = 0.0462);.;.;Gain of MoRF binding (P = 0.0462);.;Gain of MoRF binding (P = 0.0462);.;

MVP

0.84

MPC

0.35

ClinPred

0.97

GERP RS

5.2

Varity_R

0.36

gMVP

0.69

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over