6-32171310-C-T

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006411.4(AGPAT1):c.187G>A(p.Val63Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000849 in 1,613,154 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 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000061 ( 0 hom. )

Consequence

AGPAT1
NM_006411.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.29

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03628382).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGPAT1	NM_006411.4 link	c.187G>A	p.Val63Ile	missense_variant	Exon 2 of 7	ENST00000375107.8	NP_006402.1	Q99943A0A024RCV5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AGPAT1	ENST00000375107.8 link	c.187G>A	p.Val63Ile	missense_variant	Exon 2 of 7	1	NM_006411.4	ENSP00000364248.3	Q99943
PPT2-EGFL8	ENST00000422437.5 link	n.*2581C>T		non_coding_transcript_exon_variant	Exon 20 of 21	5		ENSP00000457534.1
PPT2-EGFL8	ENST00000422437.5 link	n.*2581C>T		3_prime_UTR_variant	Exon 20 of 21	5		ENSP00000457534.1

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000940

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000729

AC:

AN:

246802

Hom.:

AF XY:

0.0000446

AC XY:

AN XY:

134444

show subpopulations

Gnomad AFR exome

AF:

0.000857

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:

0.0000451

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000609

AC:

AN:

1460814

Hom.:

Cov.:

AF XY:

0.0000550

AC XY:

AN XY:

726724

show subpopulations

Gnomad4 AFR exome

AF:

0.000896

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000382

Gnomad4 NFE exome

AF:

0.0000495

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000315

AC:

AN:

152340

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.000962

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000191

Hom.:

Bravo

AF:

0.000291

ESP6500AA

AF:

0.000662

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000672

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.187G>A (p.V63I) alteration is located in exon 2 (coding exon 1) of the AGPAT1 gene. This alteration results from a G to A substitution at nucleotide position 187, causing the valine (V) at amino acid position 63 to be replaced by an isoleucine (I). 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

0.22

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

T;T;T;T;T;T

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.87

.;.;.;.;.;D

M_CAP

Uncertain

0.096

MetaRNN

Benign

0.036

T;T;T;T;T;T

MetaSVM

Uncertain

0.12

MutationAssessor

Benign

1.4

L;L;L;L;L;L

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.65

N;N;N;N;N;N

REVEL

Uncertain

0.30

Sift

Benign

0.076

T;T;T;T;T;T

Sift4G

Benign

0.13

T;T;T;T;T;T

Polyphen

0.92

P;P;P;P;P;P

Vest4

0.11

MVP

0.51

MPC

1.0

ClinPred

0.058

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.062

gMVP

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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