chr1-211749915-T-C

Position:

• chr1-211749915-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_014873.3(LPGAT1):​c.1097A>G​(p.Tyr366Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LPGAT1 NM_014873.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.89

Genes affected

LPGAT1 (HGNC:28985): (lysophosphatidylglycerol acyltransferase 1) This gene encodes a member of the lysophospholipid acyltransferase family. The encoded protein catalyzes the reacylation of lysophosphatidylglycerol to phosphatidylglycerol, a membrane phospholipid that is an important precursor for the synthesis of cardiolipin. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.774

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPGAT1	NM_014873.3	c.1097A>G	p.Tyr366Cys	missense_variant	8/8	ENST00000366997.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPGAT1	ENST00000366997.9	c.1097A>G	p.Tyr366Cys	missense_variant	8/8	1	NM_014873.3	P1
LPGAT1	ENST00000366996.1	c.1097A>G	p.Tyr366Cys	missense_variant	8/8	1		P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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 05, 2023

The c.1097A>G (p.Y366C) alteration is located in exon 8 (coding exon 7) of the LPGAT1 gene. This alteration results from a A to G substitution at nucleotide position 1097, causing the tyrosine (Y) at amino acid position 366 to be replaced by a cysteine (C). 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	0.097
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.052	T;T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.023	T
MetaRNN	Pathogenic	0.77	D;D
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.2	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.2	N;N
REVEL	Uncertain	0.33
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.022	D;D
Polyphen		1.0	D;D
Vest4		0.84
MutPred		0.65		Loss of stability (P = 0.0912);Loss of stability (P = 0.0912);
MVP		0.34
MPC		1.9
ClinPred		0.95	D
GERP RS		5.4
Varity_R		0.16
gMVP		0.78

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: chr1-211923257;