Variant 10-112155905-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000348367.9(GPAM):c.2270A>G(p.Lys757Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000603 in 1,611,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00062 ( 0 hom. )

Consequence

GPAM
ENST00000348367.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.906

Variant links:

Genes affected

GPAM (HGNC:24865): (glycerol-3-phosphate acyltransferase, mitochondrial) This gene encodes a mitochondrial enzyme which prefers saturated fatty acids as its substrate for the synthesis of glycerolipids. This metabolic pathway's first step is catalyzed by the encoded enzyme. Two forms for this enzyme exist, one in the mitochondria and one in the endoplasmic reticulum. Two alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Oct 2011]

GPAM 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=0.053212374).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPAM	NM_001244949.2 linkuse as main transcript	c.2270A>G	p.Lys757Arg	missense_variant	20/22	ENST00000348367.9	NP_001231878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPAM	ENST00000348367.9 linkuse as main transcript	c.2270A>G	p.Lys757Arg	missense_variant	20/22	1	NM_001244949.2	ENSP00000265276	P1
GPAM	ENST00000369425.5 linkuse as main transcript	c.*1332A>G		3_prime_UTR_variant	19/19	1		ENSP00000358433

Frequencies

GnomAD3 genomes

AF:

0.000401

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.000735

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000446

AC:

112

AN:

251390

Hom.:

AF XY:

0.000420

AC XY:

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000739

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000625

AC:

911

AN:

1458710

Hom.:

Cov.:

AF XY:

0.000623

AC XY:

452

AN XY:

725992

show subpopulations

Gnomad4 AFR exome

AF:

0.000240

Gnomad4 AMR exome

AF:

0.000492

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000765

Gnomad4 OTH exome

AF:

0.000481

GnomAD4 genome

AF:

0.000400

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.000403

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000735

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000636

Hom.:

Bravo

AF:

0.000412

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000428

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.00119

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 10, 2023

The c.2270A>G (p.K757R) alteration is located in exon 1 (coding exon 1) of the GPAM gene. This alteration results from a A to G substitution at nucleotide position 2270, causing the lysine (K) at amino acid position 757 to be replaced by an arginine (R). 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

0.061

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.071

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.78

M_CAP

Benign

0.012

MetaRNN

Benign

0.053

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.74

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.34

REVEL

Benign

0.045

Sift

Benign

0.64

Sift4G

Benign

0.74

Polyphen

0.0

Vest4

0.13

MVP

0.45

MPC

0.23

ClinPred

0.0039

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.020

gMVP

0.17

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