6-32169284-C-T

Position:

chr6-32169284-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_006411.4(AGPAT1):c.844G>A(p.Gly282Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,612,536 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

AGPAT1
NM_006411.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.801

Variant links:

Genes affected

AGPAT1 (HGNC:324): (1-acylglycerol-3-phosphate O-acyltransferase 1) This gene encodes an enzyme that converts lysophosphatidic acid (LPA) into phosphatidic acid (PA). LPA and PA are two phospholipids involved in signal transduction and in lipid biosynthesis in cells. This enzyme localizes to the endoplasmic reticulum. This gene is located in the class III region of the human major histocompatibility complex. Alternative splicing results in two transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

AGPAT1 links:

PPT2-EGFL8 (HGNC:48343): (PPT2-EGFL8 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring PPT2 (palmitoyl-protein thioesterase 2) and EGFL8 (EGF-like-domain, multiple 8) genes located in the major histocompatibility complex class III region of chromosome 6. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

PPT2-EGFL8 links:

AGPAT1 (HGNC:):

AGPAT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04071927).

BP6

Variant 6-32169284-C-T is Benign according to our data. Variant chr6-32169284-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3276231.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGPAT1	NM_006411.4 linkuse as main transcript	c.844G>A	p.Gly282Ser	missense_variant	7/7	ENST00000375107.8	NP_006402.1	Q99943A0A024RCV5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGPAT1	ENST00000375107.8 linkuse as main transcript	c.844G>A	p.Gly282Ser	missense_variant	7/7	1	NM_006411.4	ENSP00000364248.3		Q99943
PPT2-EGFL8	ENST00000422437.5 linkuse as main transcript	n.*1379-9C>T		intron_variant		5		ENSP00000457534.1

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000813

AC:

AN:

246122

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134144

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000181

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000233

AC:

AN:

1460452

Hom.:

Cov.:

AF XY:

0.0000262

AC XY:

AN XY:

726536

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000207

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000395

AC:

AN:

152084

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000752

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.00000846

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 21, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.41

CADD

Benign

0.88

DANN

Benign

0.74

DEOGEN2

Benign

0.0031

T;T;T;T;T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.51

.;.;.;.;.;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.041

T;T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.69

N;N;N;N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

0.25

N;N;N;N;N;N

REVEL

Benign

0.17

Sift

Benign

0.52

T;T;T;T;T;T

Sift4G

Benign

0.068

T;T;T;T;T;T

Polyphen

0.0

B;B;B;B;B;B

Vest4

0.10

MutPred

0.32

Gain of phosphorylation at G282 (P = 0.0041);Gain of phosphorylation at G282 (P = 0.0041);Gain of phosphorylation at G282 (P = 0.0041);Gain of phosphorylation at G282 (P = 0.0041);Gain of phosphorylation at G282 (P = 0.0041);Gain of phosphorylation at G282 (P = 0.0041);

MVP

0.57

MPC

1.1

ClinPred

0.033

GERP RS

-3.2

Varity_R

0.023

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

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