2-30562220-A-G

Position:

• chr2-30562220-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001002257.3(LCLAT1):​c.439A>G​(p.Met147Val) variant causes a missense change. The variant allele was found at a frequency of 0.000011 in 1,461,050 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: LCLAT1 NM_001002257.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.13

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21414647).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCLAT1	NM_001002257.3	c.439A>G	p.Met147Val	missense_variant	4/6	ENST00000379509.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCLAT1	ENST00000379509.8	c.439A>G	p.Met147Val	missense_variant	4/6	1	NM_001002257.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000110 AC: 16 AN: 1461050 Hom.: 0 Cov.: 29 AF XY: 0.0000138 AC XY: 10 AN XY: 726844

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.0000144

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

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

Oct 02, 2023

The c.553A>G (p.M185V) alteration is located in exon 5 (coding exon 4) of the LCLAT1 gene. This alteration results from a A to G substitution at nucleotide position 553, causing the methionine (M) at amino acid position 185 to be replaced by a valine (V). 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	Benign	0.12
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Benign	0.38	.;.;T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.052
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Benign	0.67	.;N;N
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.28
Sift	Benign	0.58	T;T;T
Sift4G	Benign	0.43	T;T;T
Polyphen		0.0030, 0.0010	.;B;B
Vest4		0.33
MutPred		0.49		.;Loss of disorder (P = 0.1244);Loss of disorder (P = 0.1244);
MVP		0.70
MPC		0.26
ClinPred		0.59	D
GERP RS		4.3
Varity_R		0.16
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1031698644; hg19: chr2-30785086;