Variant 10-112168443-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001244949.2(GPAM):c.976T>C(p.Cys326Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

GPAM
NM_001244949.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.634

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19042602).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPAM	NM_001244949.2 linkuse as main transcript	c.976T>C	p.Cys326Arg	missense_variant	11/22	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.976T>C	p.Cys326Arg	missense_variant	11/22	1	NM_001244949.2	ENSP00000265276	P1
GPAM	ENST00000369425.5 linkuse as main transcript	c.976T>C	p.Cys326Arg	missense_variant	11/19	1		ENSP00000358433

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251412

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135884

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:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1460106

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726494

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000756

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

Jul 25, 2023

The c.976T>C (p.C326R) alteration is located in exon 1 (coding exon 1) of the GPAM gene. This alteration results from a T to C substitution at nucleotide position 976, causing the cysteine (C) at amino acid position 326 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

0.10

BayesDel_addAF

Benign

-0.0061

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.36

T;.

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.057

MetaRNN

Benign

0.19

T;T

MetaSVM

Uncertain

-0.15

MutationAssessor

Benign

0.14

N;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.4

N;N

REVEL

Uncertain

0.29

Sift

Benign

0.41

T;T

Sift4G

Benign

0.065

T;T

Polyphen

0.0

B;B

Vest4

0.25

MutPred

0.54

Gain of disorder (P = 0.0043);Gain of disorder (P = 0.0043);

MVP

0.58

MPC

0.49

ClinPred

0.16

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.36

gMVP

0.89

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