Variant 8-6730725-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_018361.5(AGPAT5):c.304G>T(p.Ala102Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,612,998 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 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

AGPAT5
NM_018361.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.88

Variant links:

Genes affected

AGPAT5 (HGNC:20886): (1-acylglycerol-3-phosphate O-acyltransferase 5) 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. A pseudogene of this gene is present on the Y chromosome. [provided by RefSeq, Aug 2014]

AGPAT5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
AGPAT5	NM_018361.5 linkuse as main transcript	c.304G>T	p.Ala102Ser	missense_variant	3/8	ENST00000285518.11
AGPAT5	XM_047421940.1 linkuse as main transcript	c.304G>T	p.Ala102Ser	missense_variant	3/5
AGPAT5	XM_047421938.1 linkuse as main transcript	c.-150G>T		5_prime_UTR_variant	2/7
AGPAT5	XM_047421939.1 linkuse as main transcript	c.-150G>T		5_prime_UTR_variant	4/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
AGPAT5	ENST00000285518.11 linkuse as main transcript	c.304G>T	p.Ala102Ser	missense_variant	3/8	1	NM_018361.5	P1
AGPAT5	ENST00000518327.1 linkuse as main transcript	c.195+21838G>T		intron_variant		1
AGPAT5	ENST00000523234.5 linkuse as main transcript	c.234G>T	p.Leu78Phe	missense_variant, NMD_transcript_variant	2/7	5
AGPAT5	ENST00000523586.1 linkuse as main transcript	c.*236G>T		3_prime_UTR_variant, NMD_transcript_variant	4/4	4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152166

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:

0.000193

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:

0.0000438

AC:

AN:

251350

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000599

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460832

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726736

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000494

AC:

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

Feb 28, 2023

The c.304G>T (p.A102S) alteration is located in exon 3 (coding exon 3) of the AGPAT5 gene. This alteration results from a G to T substitution at nucleotide position 304, causing the alanine (A) at amino acid position 102 to be replaced by a serine (S). 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

0.27

BayesDel_addAF

Uncertain

0.093

BayesDel_noAF

Pathogenic

0.23

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.53

Eigen

Benign

-0.077

Eigen_PC

Benign

0.053

FATHMM_MKL

Pathogenic

0.98

M_CAP

Benign

0.053

MetaRNN

Benign

0.32

MetaSVM

Uncertain

0.57

MutationAssessor

Benign

1.5

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.59

Sift

Uncertain

0.012

Sift4G

Benign

0.063

Polyphen

0.0010

Vest4

0.60

MutPred

0.59

Loss of helix (P = 0.2022);

MVP

0.93

MPC

0.024

ClinPred

0.23

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.30

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.24

Position offset: -14

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