6-161232086-T-G

Position:

• chr6-161232086-T-G

Variant summary

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

The NM_020133.3(AGPAT4):​c.128A>C​(p.Lys43Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AGPAT4 NM_020133.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.28

Genes affected

AGPAT4 (HGNC:20885): (1-acylglycerol-3-phosphate O-acyltransferase 4) This gene encodes a member of the 1-acylglycerol-3-phosphate O-acyltransferase family. This integral membrane protein converts lysophosphatidic acid to phosphatidic acid, the second step in de novo phospholipid biosynthesis. [provided by RefSeq, Jul 2008]

ACMG classification

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
AGPAT4	NM_020133.3	c.128A>C	p.Lys43Thr	missense_variant	2/9	ENST00000320285.9	NP_064518.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGPAT4	ENST00000320285.9	c.128A>C	p.Lys43Thr	missense_variant	2/9	1	NM_020133.3	ENSP00000314036	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Mar 04, 2024

The c.128A>C (p.K43T) alteration is located in exon 2 (coding exon 1) of the AGPAT4 gene. This alteration results from a A to C substitution at nucleotide position 128, causing the lysine (K) at amino acid position 43 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	Pathogenic	0.70
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T;T;T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.62	D;D;D
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.7	.;M;.
MutationTaster	Benign	1.0	D;D;D;D;D;N
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-4.6	D;D;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0010	D;D;T
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		1.0	.;D;.
Vest4		0.66
MutPred		0.50		Loss of methylation at K43 (P = 0.0101);Loss of methylation at K43 (P = 0.0101);Loss of methylation at K43 (P = 0.0101);
MVP		0.33
MPC		1.7
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.49
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr6-161653118;