10-112166426-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001244949.2(GPAM):c.1197T>C(p.Asp399=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00372 in 1,602,358 control chromosomes in the GnomAD database, including 211 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (111 hom., cov: 33)
  • Exomes 𝑓: 0.0020 (100 hom.)
• Consequence: GPAM NM_001244949.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.117

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

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 10-112166426-A-G is Benign according to our data. Variant chr10-112166426-A-G is described in ClinVar as [Benign]. Clinvar id is 776543.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.117 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPAM	NM_001244949.2	c.1197T>C	p.Asp399=	synonymous_variant	12/22	ENST00000348367.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPAM	ENST00000348367.9	c.1197T>C	p.Asp399=	synonymous_variant	12/22	1	NM_001244949.2	P1
GPAM	ENST00000369425.5	c.1197T>C	p.Asp399=	synonymous_variant	12/19	1

Frequencies

GnomAD3 genomes AF: 0.0201 AC: 3063 AN: 152144 Hom.: 111 Cov.: 33

Gnomad AFR AF: 0.0699

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00831

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: 0.000162

Gnomad OTH AF: 0.0129

GnomAD3 exomes AF: 0.00511 AC: 1286 AN: 251418 Hom.: 37 AF XY: 0.00368 AC XY: 500 AN XY: 135886

Gnomad AFR exome AF: 0.0706

Gnomad AMR exome AF: 0.00289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.00228

GnomAD4 exome AF: 0.00200 AC: 2902 AN: 1450096 Hom.: 100 Cov.: 28 AF XY: 0.00173 AC XY: 1247 AN XY: 722354

Gnomad4 AFR exome AF: 0.0716

Gnomad4 AMR exome AF: 0.00335

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000999

Gnomad4 OTH exome AF: 0.00397

GnomAD4 genome AF: 0.0201 AC: 3062 AN: 152262 Hom.: 111 Cov.: 33 AF XY: 0.0198 AC XY: 1475 AN XY: 74460

Gnomad4 AFR AF: 0.0697

Gnomad4 AMR AF: 0.00830

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00918 Hom.: 32

Bravo AF: 0.0233

Asia WGS AF: 0.00260 AC: 10 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 23, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	6.1
Dann	Benign	0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs34047745; hg19: chr10-113926184;