Variant 6-161139592-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_020133.3(AGPAT4):c.872C>T(p.Thr291Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000143 in 1,612,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

AGPAT4
NM_020133.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.54

Variant links:

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]

AGPAT4 links:

LOC124901455 (HGNC:):

LOC124901455 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29244727).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGPAT4	NM_020133.3 linkuse as main transcript	c.872C>T	p.Thr291Met	missense_variant	8/9	ENST00000320285.9	NP_064518.1
LOC124901455	XR_007059860.1 linkuse as main transcript			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGPAT4	ENST00000320285.9 linkuse as main transcript	c.872C>T	p.Thr291Met	missense_variant	8/9	1	NM_020133.3	ENSP00000314036	P1	Q9NRZ5-1
AGPAT4	ENST00000366911.9 linkuse as main transcript	c.*345C>T		3_prime_UTR_variant	7/8	1		ENSP00000355878

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000798

AC:

AN:

250476

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135392

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000997

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1460472

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

726310

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152110

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000387

Hom.:

Bravo

AF:

0.00000756

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 18, 2023

The c.872C>T (p.T291M) alteration is located in exon 8 (coding exon 7) of the AGPAT4 gene. This alteration results from a C to T substitution at nucleotide position 872, causing the threonine (T) at amino acid position 291 to be replaced by a methionine (M). 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

0.11

BayesDel_addAF

Benign

-0.047

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.27

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.81

M_CAP

Benign

0.073

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.74

MutationAssessor

Uncertain

2.9

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.17

Sift

Uncertain

0.0060

Sift4G

Benign

0.086

Polyphen

1.0

Vest4

0.45

MutPred

0.30

Gain of catalytic residue at T291 (P = 0.0384);

MVP

0.29

MPC

1.7

ClinPred

0.96

GERP RS

3.3

Varity_R

0.18

gMVP

0.50

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over