6-161146534-T-A

Position:

• chr6-161146534-T-A

Variant summary

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

The NM_020133.3(AGPAT4):​c.833A>T​(p.Tyr278Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AGPAT4 NM_020133.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.70

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]

LOC124901455 (HGNC:):

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.833A>T	p.Tyr278Phe	missense_variant	7/9	ENST00000320285.9	NP_064518.1
LOC124901455	XR_007059860.1	n.6308T>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGPAT4	ENST00000320285.9	c.833A>T	p.Tyr278Phe	missense_variant	7/9	1	NM_020133.3	ENSP00000314036.4
AGPAT4	ENST00000366911.9	c.*306A>T		3_prime_UTR_variant	6/8	1		ENSP00000355878.5
AGPAT4	ENST00000437165.1	c.167A>T	p.Tyr56Phe	missense_variant	2/3	5		ENSP00000400211.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Oct 20, 2024

The c.833A>T (p.Y278F) alteration is located in exon 7 (coding exon 6) of the AGPAT4 gene. This alteration results from a A to T substitution at nucleotide position 833, causing the tyrosine (Y) at amino acid position 278 to be replaced by a phenylalanine (F). 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	0.25
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	26
DANN	Benign	0.97
DEOGEN2	Benign	0.093	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.091	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Uncertain	0.29	D
MutationAssessor	Benign	1.8	L
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.5	N
REVEL	Pathogenic	0.69
Sift	Benign	0.46	T
Sift4G	Benign	0.34	T
Polyphen		1.0	D
Vest4		0.62
MutPred		0.66		Loss of ubiquitination at K276 (P = 0.0653);
MVP		0.56
MPC		0.89
ClinPred		0.91	D
GERP RS		5.0
Varity_R		0.30
gMVP		0.56

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: chr6-161567566;