10-112159925-C-T

Variant summary

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

The NM_001244949.2(GPAM):​c.1888G>A​(p.Gly630Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

GPAM
NM_001244949.2 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.80
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]

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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 rank MANE Protein UniProt
GPAMNM_001244949.2 linkc.1888G>A p.Gly630Ser missense_variant Exon 17 of 22 ENST00000348367.9 NP_001231878.1 Q9HCL2Q8N1G6Q86T70

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GPAMENST00000348367.9 linkc.1888G>A p.Gly630Ser missense_variant Exon 17 of 22 1 NM_001244949.2 ENSP00000265276.4 Q9HCL2
GPAMENST00000369425.5 linkc.1888G>A p.Gly630Ser missense_variant Exon 17 of 19 1 ENSP00000358433.1 Q5VW52

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 07, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1888G>A (p.G630S) alteration is located in exon 1 (coding exon 1) of the GPAM gene. This alteration results from a G to A substitution at nucleotide position 1888, causing the glycine (G) at amino acid position 630 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
0.12
BayesDel_addAF
Benign
0.00081
T
BayesDel_noAF
Benign
-0.24
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.059
T;.
Eigen
Uncertain
0.31
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.90
D;D
M_CAP
Benign
0.042
D
MetaRNN
Uncertain
0.46
T;T
MetaSVM
Benign
-0.37
T
MutationAssessor
Benign
1.7
L;.
PrimateAI
Uncertain
0.54
T
PROVEAN
Benign
0.070
N;N
REVEL
Benign
0.26
Sift
Benign
0.50
T;T
Sift4G
Benign
0.53
T;T
Polyphen
0.63
P;P
Vest4
0.47
MutPred
0.60
Gain of catalytic residue at G630 (P = 0.0492);Gain of catalytic residue at G630 (P = 0.0492);
MVP
0.72
MPC
0.41
ClinPred
0.74
D
GERP RS
5.0
Varity_R
0.10
gMVP
0.53

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-113919683; API