NM_001244949.2:c.1259C>T

Variant names:

• chr10-112164573-G-A
• rs73365184
• NM_001244949.2:c.1259C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001244949.2(GPAM):​c.1259C>T​(p.Ala420Val) variant causes a missense change. The variant allele was found at a frequency of 0.00338 in 1,607,080 control chromosomes in the GnomAD database, including 172 homozygotes. 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (84 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (88 hom.)
• Consequence: GPAM NM_001244949.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.99
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0026896).
• BP6: Variant 10-112164573-G-A is Benign according to our data. Variant chr10-112164573-G-A is described in ClinVar as Benign. ClinVar VariationId is 776541.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0609 is higher than 0.05.

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.1259C>T	p.Ala420Val	missense	Exon 13 of 22	NP_001231878.1	Q9HCL2
	GPAM	NM_020918.6		c.1259C>T	p.Ala420Val	missense	Exon 13 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.1259C>T	p.Ala420Val	missense	Exon 13 of 22	ENSP00000265276.4	Q9HCL2
	GPAM	ENST00000369425.5	TSL:1	c.1259C>T	p.Ala420Val	missense	Exon 13 of 19	ENSP00000358433.1	Q5VW52
	GPAM	ENST00000964625.1		c.1259C>T	p.Ala420Val	missense	Exon 13 of 22	ENSP00000634684.1

Frequencies

GnomAD3 genomes AF: 0.0182 AC: 2774 AN: 152184 Hom.: 84 Cov.: 32

Gnomad AFR AF: 0.0631

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00798

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.00455 AC: 1144 AN: 251322 AF XY: 0.00322

Gnomad AFR exome AF: 0.0630

Gnomad AMR exome AF: 0.00246

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000167

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.00183 AC: 2658 AN: 1454778 Hom.: 88 Cov.: 27 AF XY: 0.00156 AC XY: 1128 AN XY: 724254

African (AFR) AF: 0.0650 AC: 2162 AN: 33258

American (AMR) AF: 0.00300 AC: 134 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26080

East Asian (EAS) AF: 0.00 AC: 0 AN: 39626

South Asian (SAS) AF: 0.000151 AC: 13 AN: 86132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00278 AC: 16 AN: 5750

European-Non Finnish (NFE) AF: 0.0000986 AC: 109 AN: 1105702

Other (OTH) AF: 0.00373 AC: 224 AN: 60112

GnomAD4 genome AF: 0.0182 AC: 2772 AN: 152302 Hom.: 84 Cov.: 32 AF XY: 0.0180 AC XY: 1340 AN XY: 74476

African (AFR) AF: 0.0629 AC: 2613 AN: 41556

American (AMR) AF: 0.00797 AC: 122 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68024

Other (OTH) AF: 0.0114 AC: 24 AN: 2114

Alfa AF: 0.00690 Hom.: 69

Bravo AF: 0.0212

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0633 AC: 279

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00550 AC: 668

Asia WGS AF: 0.00260 AC: 10 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.80	T
MetaRNN	Benign	0.0027	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.1	L
PhyloP100		4.0
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.14
Sift	Benign	0.060	T
Sift4G	Benign	0.78	T
Polyphen		0.0010	B
Vest4		0.20
MVP		0.66
MPC		0.28
ClinPred		0.026	T
GERP RS		4.3
Varity_R		0.099
gMVP		0.31
Mutation Taster		=96/4	polymorphism (auto)

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: rs73365184; hg19: chr10-113924331; COSMIC: COSV105909561;