1-211751029-T-C

Position:

• chr1-211751029-T-C

Variant summary

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

The NM_014873.3(LPGAT1):​c.893A>G​(p.Asp298Gly) 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. 16/21 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: LPGAT1 NM_014873.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.57

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.075127274).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPGAT1	NM_014873.3	c.893A>G	p.Asp298Gly	missense_variant	7/8	ENST00000366997.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPGAT1	ENST00000366997.9	c.893A>G	p.Asp298Gly	missense_variant	7/8	1	NM_014873.3	P1
LPGAT1	ENST00000366996.1	c.893A>G	p.Asp298Gly	missense_variant	7/8	1		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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

Sep 25, 2023

The c.893A>G (p.D298G) alteration is located in exon 7 (coding exon 6) of the LPGAT1 gene. This alteration results from a A to G substitution at nucleotide position 893, causing the aspartic acid (D) at amino acid position 298 to be replaced by a glycine (G). 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	0.068
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Benign	0.91
DEOGEN2	Benign	0.022	T;T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.52	D
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.075	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;N
MutationTaster	Benign	0.70	N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.19	N;N
REVEL	Benign	0.071
Sift	Benign	0.27	T;T
Sift4G	Benign	0.36	T;T
Polyphen		0.0	B;B
Vest4		0.086
MutPred		0.27		Loss of stability (P = 0.0853);Loss of stability (P = 0.0853);
MVP		0.15
MPC		0.88
ClinPred		0.16	T
GERP RS		1.1
Varity_R		0.063
gMVP		0.57

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: chr1-211924371;