10-112163799-T-C

Variant names:

• chr10-112163799-T-C
• rs148432598
• NM_001244949.2:c.1325A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001244949.2(GPAM):​c.1325A>G​(p.Asp442Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000244 in 1,575,318 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00024 (2 hom.)
• Consequence: GPAM NM_001244949.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.914
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0062708557).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001244949.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPAM	NM_001244949.2	MANE Select	c.1325A>G	p.Asp442Gly	missense	Exon 14 of 22	NP_001231878.1	Q9HCL2
	GPAM	NM_020918.6		c.1325A>G	p.Asp442Gly	missense	Exon 14 of 22	NP_065969.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPAM	ENST00000348367.9	TSL:1 MANE Select	c.1325A>G	p.Asp442Gly	missense	Exon 14 of 22	ENSP00000265276.4	Q9HCL2
	GPAM	ENST00000369425.5	TSL:1	c.1325A>G	p.Asp442Gly	missense	Exon 14 of 19	ENSP00000358433.1	Q5VW52
	GPAM	ENST00000964625.1		c.1325A>G	p.Asp442Gly	missense	Exon 14 of 22	ENSP00000634684.1

Frequencies

GnomAD3 genomes AF: 0.000315 AC: 48 AN: 152220 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000426 AC: 107 AN: 251222 AF XY: 0.000412

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00893

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000968

Gnomad OTH exome AF: 0.000816

GnomAD4 exome AF: 0.000237 AC: 337 AN: 1423098 Hom.: 2 Cov.: 25 AF XY: 0.000256 AC XY: 182 AN XY: 710494

African (AFR) AF: 0.0000306 AC: 1 AN: 32688

American (AMR) AF: 0.00 AC: 0 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.00931 AC: 241 AN: 25894

East Asian (EAS) AF: 0.00 AC: 0 AN: 39484

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85490

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5700

European-Non Finnish (NFE) AF: 0.0000511 AC: 55 AN: 1076680

Other (OTH) AF: 0.000643 AC: 38 AN: 59110

GnomAD4 genome AF: 0.000315 AC: 48 AN: 152220 Hom.: 0 Cov.: 33 AF XY: 0.000403 AC XY: 30 AN XY: 74382

African (AFR) AF: 0.00 AC: 0 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0121 AC: 42 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5206

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000981 Hom.: 0

Bravo AF: 0.000287

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000329 AC: 40

EpiCase AF: 0.000273

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	13
DANN	Benign	0.67
DEOGEN2	Benign	0.075	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.79
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.0063	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.91
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.068
Sift	Benign	0.55	T
Sift4G	Benign	0.33	T
Polyphen		0.0020	B
Vest4		0.28
MVP		0.20
MPC		0.37
ClinPred		0.0099	T
GERP RS		-0.96
Varity_R		0.040
gMVP		0.36
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs148432598; hg19: chr10-113923557;