chr2-30640534-T-C

Position:

• chr2-30640534-T-C

Variant summary

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

The NM_001002257.3(LCLAT1):​c.1046T>C​(p.Ile349Thr) 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. 13/21 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)
• Consequence: LCLAT1 NM_001002257.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.57

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=0.2302804).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LCLAT1	NM_001002257.3	c.1046T>C	p.Ile349Thr	missense_variant	6/6	ENST00000379509.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LCLAT1	ENST00000379509.8	c.1046T>C	p.Ile349Thr	missense_variant	6/6	1	NM_001002257.3	P1
LCLAT1	ENST00000309052.8	c.1160T>C	p.Ile387Thr	missense_variant	7/7	1
LCLAT1	ENST00000491680.6	n.1197T>C		non_coding_transcript_exon_variant	6/6	2
LCLAT1	ENST00000478015.5	c.*1193T>C		3_prime_UTR_variant, NMD_transcript_variant	8/8	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

Jun 07, 2023

The c.1160T>C (p.I387T) alteration is located in exon 7 (coding exon 6) of the LCLAT1 gene. This alteration results from a T to C substitution at nucleotide position 1160, causing the isoleucine (I) at amino acid position 387 to be replaced by a threonine (T). 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	0.32
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.12	.;T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.032
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	.;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.51	N;N
REVEL	Benign	0.17
Sift	Benign	0.17	T;T
Sift4G	Benign	0.47	T;T
Polyphen		0.36	.;B
Vest4		0.28
MutPred		0.61		.;Loss of stability (P = 0.0051);
MVP		0.45
MPC		0.32
ClinPred		0.50	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.071
gMVP		0.35

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-30863400;