6-161154241-C-T

Variant names:

• chr6-161154241-C-T
• NM_020133.3:c.418G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020133.3(AGPAT4):​c.418G>A​(p.Glu140Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: AGPAT4 NM_020133.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.69
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.93

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020133.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGPAT4	NM_020133.3	MANE Select	c.418G>A	p.Glu140Lys	missense	Exon 4 of 9	NP_064518.1	Q9NRZ5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGPAT4	ENST00000320285.9	TSL:1 MANE Select	c.418G>A	p.Glu140Lys	missense	Exon 4 of 9	ENSP00000314036.4	Q9NRZ5-1
	AGPAT4	ENST00000436279.1	TSL:1	n.*153G>A		non_coding_transcript_exon	Exon 4 of 6	ENSP00000413901.1	G3XAF1
	AGPAT4	ENST00000436279.1	TSL:1	n.*153G>A		3_prime_UTR	Exon 4 of 6	ENSP00000413901.1	G3XAF1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461884 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.48	D
BayesDel_noAF	Pathogenic	0.45
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.68	D
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		7.7
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.6	D
REVEL	Pathogenic	0.85
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.98	D
Vest4		0.88
MutPred		0.68		Gain of MoRF binding (P = 0.0016)
MVP		0.92
MPC		1.8
ClinPred		1.0	D
GERP RS		4.3
Varity_R		0.72
gMVP		0.99
Mutation Taster		=45/55	disease causing

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

Other links and lift over

hg19: chr6-161575273; COSMIC: COSV57245187; COSMIC: COSV57245187;